1  6679 195 USING MACHINE LEARNING TO PREDICT OBESITY BASED ON GENOME-WIDE AND EPIGENOME-WIDE GENE-GENE AND GENE-DIET INTERACTIONS. OBESITY IS ASSOCIATED WITH MANY CHRONIC DISEASES THAT IMPAIR HEALTHY AGING AND IS GOVERNED BY GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS AND THEIR COMPLEX INTERACTIONS. THIS STUDY AIMED TO DEVELOP A MODEL THAT PREDICTS AN INDIVIDUAL'S RISK OF OBESITY BY BETTER CHARACTERIZING THESE COMPLEX RELATIONS AND INTERACTIONS FOCUSING ON DIETARY FACTORS. FOR THIS PURPOSE, WE CONDUCTED A COMBINED GENOME-WIDE AND EPIGENOME-WIDE SCAN FOR BODY MASS INDEX (BMI) AND UP TO THREE-WAY INTERACTIONS AMONG 402,793 SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS), 415,202 DNA METHYLATION SITES (DMSS), AND 397 DIETARY AND LIFESTYLE FACTORS USING THE GENERALIZED MULTIFACTOR DIMENSIONALITY REDUCTION (GMDR) METHOD. THE TRAINING SET CONSISTED OF 1,573 PARTICIPANTS IN EXAM 8 OF THE FRAMINGHAM OFFSPRING STUDY (FOS) COHORT. AFTER IDENTIFYING GENETIC, EPIGENETIC, AND DIETARY FACTORS THAT PASSED STATISTICAL SIGNIFICANCE, WE APPLIED MACHINE LEARNING (ML) ALGORITHMS TO PREDICT PARTICIPANTS' OBESITY STATUS IN THE TEST SET, TAKEN AS A SUBSET OF INDEPENDENT SAMPLES (N = 394) FROM THE SAME COHORT. THE QUALITY AND ACCURACY OF PREDICTION MODELS WERE EVALUATED USING THE AREA UNDER THE RECEIVER OPERATING CHARACTERISTIC CURVE (ROC-AUC). GMDR IDENTIFIED 213 SNPS, 530 DMSS, AND 49 DIETARY AND LIFESTYLE FACTORS AS SIGNIFICANT PREDICTORS OF OBESITY. COMPARING SEVERAL ML ALGORITHMS, WE FOUND THAT THE STOCHASTIC GRADIENT BOOSTING MODEL PROVIDED THE BEST PREDICTION ACCURACY FOR OBESITY WITH AN OVERALL ACCURACY OF 70%, WITH ROC-AUC OF 0.72 IN TEST SET SAMPLES. TOP PREDICTORS OF THE BEST-FIT MODEL WERE 21 SNPS, 230 DMSS IN GENES SUCH AS CPT1A, ABCG1, SLC7A11, RNF145, AND SREBF1, AND 26 DIETARY FACTORS, INCLUDING PROCESSED MEAT, DIET SODA, FRENCH FRIES, HIGH-FAT DAIRY, ARTIFICIAL SWEETENERS, ALCOHOL INTAKE, AND SPECIFIC NUTRIENTS AND FOOD COMPONENTS, SUCH AS CALCIUM AND FLAVONOLS. IN CONCLUSION, WE DEVELOPED AN INTEGRATED APPROACH WITH ML TO PREDICT OBESITY USING OMICS AND DIETARY DATA. THIS EXTENDS OUR KNOWLEDGE OF THE DRIVERS OF OBESITY, WHICH CAN INFORM PRECISION NUTRITION STRATEGIES FOR THE PREVENTION AND TREATMENT OF OBESITY. CLINICAL TRIAL REGISTRATION: [WWW.CLINICALTRIALS.GOV], THE FRAMINGHAM HEART STUDY (FHS), [NCT00005121].	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
2  2777  35 EXTREMELY LOW BIRTH WEIGHT AND ACCELERATED BIOLOGICAL AGING. BACKGROUND AND OBJECTIVES: EXTREMELY LOW BIRTH WEIGHT (ELBW) (<1000 G) SURVIVORS ARE EXPOSED TO ELEVATED LEVELS OF PHYSIOLOGIC STRESS DURING THEIR LIVES AND MAY BE SUSCEPTIBLE TO ACCELERATED AGING. USING THE OLDEST KNOWN LONGITUDINALLY FOLLOWED COHORT OF ELBW SURVIVORS, WE COMPARED BIOLOGICAL AGING IN THIS GROUP USING AN EPIGENETIC CLOCK TO A SAMPLE OF MATCHED NORMAL BIRTH WEIGHT (NBW) (>2500 G) CONTROL PARTICIPANTS. METHODS: BUCCAL CELLS WERE COLLECTED FROM 45 ELBW SURVIVORS AND 49 NBW CONTROL PARTICIPANTS AT 30 TO 35 YEARS OF AGE. EPIGENETIC AGE WAS CALCULATED FROM THE WEIGHTED AVERAGE OF DNA METHYLATION AT 353 CYTOSINE-PHOSPHATE-GUANINE SEQUENCE WITHIN DNA SITES, BY USING THE ILLUMINA INFINIUM HUMAN METHYLATION EPIC 850K BEADCHIP ARRAY. RESULTS: BEFORE AND AFTER STATISTICALLY ADJUSTING FOR NEUROSENSORY IMPAIRMENT AND THE PRESENCE OF CHRONIC HEALTH CONDITIONS, A SIGNIFICANT SEX BY BIRTH WEIGHT GROUP INTERACTION WAS OBSERVED IN THE 353-SITE EPIGENETIC-CLOCK ASSAY (P = .03), WHEREBY ELBW MEN HAD A SIGNIFICANTLY OLDER EPIGENETIC AGE THAN NBW MEN (4.6 YEARS; P = .01). WOMEN BORN AT ELBW WERE NOT FOUND TO BE EPIGENETICALLY OLDER THAN THEIR NBW PEERS. CONCLUSIONS: THE RESULTS OF THIS STUDY SUGGEST THAT PRENATAL EXPOSURES MAY PLAY AN IMPORTANT ROLE IN AGING, AND THAT MEN BORN PRETERM MAY EXPERIENCE ACCELERATED AGING RELATIVE TO THEIR PEERS. WE FURTHER HIGHLIGHT THE NEED TO MONITOR AND PROMOTE THE HEALTH OF PRETERM SURVIVORS, WITH A PARTICULAR FOCUS ON HEALTHY AGING ACROSS THE LIFE SPAN.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
3  5395  40 REDUCED EPIGENETIC AGE IN OLDER ADULTS WITH HIGH SENSE OF PURPOSE IN LIFE. PSYCHOSOCIAL RISK FACTORS HAVE BEEN LINKED WITH ACCELERATED EPIGENETIC AGING, BUT LITTLE IS KNOWN ABOUT WHETHER PSYCHOSOCIAL RESILIENCE FACTORS (EG, SENSE OF PURPOSE IN LIFE) MIGHT REDUCE EPIGENETIC AGE ACCELERATION. IN THIS STUDY, WE TESTED IF OLDER ADULTS WHO EXPERIENCE HIGH LEVELS OF PURPOSE MIGHT SHOW REDUCED EPIGENETIC AGE ACCELERATION. WE EVALUATED THE RELATIONSHIP BETWEEN PURPOSE AND EPIGENETIC AGE ACCELERATION AS MEASURED BY 13 DNA METHYLATION (DNAM) "EPIGENETIC CLOCKS" ASSESSED IN 1 572 OLDER ADULTS FROM THE HEALTH AND RETIREMENT STUDY (MEAN AGE 70 YEARS). WE QUANTIFIED THE TOTAL ASSOCIATION BETWEEN PURPOSE AND DNAM AGE ACCELERATION AS WELL AS THE EXTENT TO WHICH THAT TOTAL ASSOCIATION MIGHT BE ATTRIBUTABLE TO DEMOGRAPHIC FACTORS, CHRONIC DISEASE, OTHER PSYCHOSOCIAL VARIABLES (EG, POSITIVE AFFECT), AND HEALTH-RELATED BEHAVIORS (HEAVY DRINKING, SMOKING, PHYSICAL ACTIVITY, AND BODY MASS INDEX [BMI]). PURPOSE IN LIFE WAS ASSOCIATED WITH REDUCED EPIGENETIC AGE ACCELERATION ACROSS 4 "SECOND-GENERATION" DNAM CLOCKS OPTIMIZED FOR PREDICTING HEALTH AND LONGEVITY (FALSE DISCOVERY RATE [FDR] Q < 0.0001: PHENOAGE, GRIMAGE, ZHANG EPIGENETIC MORTALITY INDEX; FDR Q < 0.05: DUNEDINPOAM). THESE ASSOCIATIONS WERE INDEPENDENT OF DEMOGRAPHIC AND PSYCHOSOCIAL FACTORS, BUT SUBSTANTIALLY ATTENUATED AFTER ADJUSTING FOR HEALTH-RELATED BEHAVIORS (DRINKING, SMOKING, PHYSICAL ACTIVITY, AND BMI). PURPOSE SHOWED NO SIGNIFICANT ASSOCIATION WITH 9 "FIRST-GENERATION" DNAM EPIGENETIC CLOCKS TRAINED ON CHRONOLOGICAL AGE. OLDER ADULTS WITH GREATER PURPOSE IN LIFE SHOW "YOUNGER" DNAM EPIGENETIC AGE ACCELERATION. THESE RESULTS MAY BE DUE IN PART TO ASSOCIATED DIFFERENCES IN HEALTH-RELATED BEHAVIORS. RESULTS SUGGEST NEW OPPORTUNITIES TO REDUCE BIOLOGICAL AGE ACCELERATION BY ENHANCING PURPOSE AND ITS BEHAVIORAL SEQUELAE IN LATE ADULTHOOD.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
4  3850  33 IS GENDER A FACTOR AFFECTING LONG-TERM HETEROTOPIC OSSIFICATION INCIDENCE AFTER SINGLE-LEVEL CERVICAL DISC ARTHROPLASTY? BACKGROUND: CERVICAL DISC DISEASES HAVE BEEN TREATED BY CERVICAL DISC ARTHROPLASTY (CDA). NEVERTHELESS, SOME PATIENTS WILL EXPERIENCE A MOBILITY FAILURE IN THEIR CERVICAL PROSTHESES OVER TIME BECAUSE OF HETEROTOPIC OSSIFICATION. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE ROLE OF GENDER IN LONG-TERM OUTCOMES AFTER CDA. METHODS: A RETROSPECTIVE, SINGLE-CENTER STUDY OF PATIENTS WHO UNDERWENT SINGLE-LEVEL CDA WITH A BRYAN CERVICAL DISC PROSTHESIS WAS PERFORMED, INCLUDING A NARRATIVE REVIEW ABOUT GENDER DIFFERENCES IN BOTH STRUCTURAL AND BIOMECHANICAL FEATURES OF THE CERVICAL SPINE. RESULTS: STUDY PATIENTS (14 MEN, 30 WOMEN) HAD AN AVERAGE FOLLOW-UP OF 9.8 +/- 3.2 YEARS. SIGNIFICANT DIFFERENCES EMERGED BETWEEN GENDERS FOR SPECIFIC ITEMS IN NECK DISABILITY INDEX PREOPERATIVE EVALUATION, WITH WOMEN REPORTING WORSE PAIN SCORES (P = 0.05). AFTER STRATIFICATION BY AGE, WE FOUND A HIGHER PREOPERATIVE OVERALL NECK DISABILITY INDEX SCORE FOR FEMALE PATIENTS <36 YEARS OF AGE (P = 0.03). IN AN INTERGENDER, BODY MASS INDEX-SPECIFIC COMPARISON, WE ALSO FOUND A SIGNIFICANT DIFFERENCE IN NECK DISABILITY INDEX PREOPERATIVE SCORE WITH NORMAL-WEIGHT MALE PATIENTS FARING WORSE THAN OVERWEIGHT MALE PATIENTS (P = 0.05). AT A RADIOLOGICAL LEVEL, WE FOUND A TENDENCY TOWARD A HIGHER HETEROTOPIC OSSIFICATION INCIDENCE IN MALE PATIENTS (62% IN MEN, 17% IN WOMEN, P = 0.06). THE FEMALE CERVICAL SPINE HAS DISTINCTIVE FEATURES, INCLUDING BONE STRUCTURE, MUSCULAR ACTION, SOFT TISSUE RESPONSE, AND GENETIC AND EPIGENETIC RESPONSE TO OSTEOARTHRITIS. CONCLUSIONS: THE INCIDENCE OF MOBILITY FAILURE IN OUR SERIES OF SINGLE-LEVEL CDA WAS LOWER IN FEMALE PATIENTS. SEVERAL GENDER-SPECIFIC FACTORS BOTH IN STATIC AND IN DYNAMIC FEATURES MAY PLAY A SIGNIFICANT ROLE IN SPINAL PATHOLOGY AND CDA LONG-TERM RADIOLOGICAL OUTCOME.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
5  3179  38 HAIR CORTISOL AS A HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BIOMARKER IN PREGNANT WOMEN WITH ASTHMA: A RETROSPECTIVE OBSERVATIONAL STUDY. BACKGROUND: CORTISOL IS A HORMONE INVOLVED IN MANY PHYSIOLOGICAL FUNCTIONS INCLUDING FETAL MATURATION AND EPIGENETIC PROGRAMMING DURING PREGNANCY. THIS STUDY AIMED TO USE HAIR CORTISOL AS A BIOMARKER OF CHRONIC INHALED CORTICOSTEROID (ICS) EXPOSURE AND ASSESS THE POTENTIAL EFFECTS OF ASTHMA ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN PREGNANT WOMEN. WE HYPOTHESIZED THAT PREGNANT WOMEN WITH ASTHMA TREATED WITH ICS WOULD EXHIBIT LOWER HAIR CORTISOL CONCENTRATIONS, INDICATIVE OF ADRENAL SUPPRESSION, COMPARED TO WOMEN WITH ASTHMA NOT USING ICS AND WOMEN WHO DO NOT HAVE ASTHMA. METHODS: WE PERFORMED AN OBSERVATIONAL RETROSPECTIVE COHORT STUDY. HAIR SAMPLES WERE ANALYZED FROM PREGNANT WOMEN WITH ASTHMA, WITH (N = 56) AND WITHOUT (N = 31) ICS TREATMENT, AND PREGNANT WOMEN WITHOUT ASTHMA (N = 31). HAIR SAMPLES WERE SEGMENTED BASED ON THE GROWTH RATE OF 1 CM/MONTH AND ANALYZED BY ENZYME IMMUNOASSAY TO PROVIDE CORTISOL CONCENTRATIONS CORRESPONDING TO PRECONCEPTION, TRIMESTERS 1-3, AND POSTPARTUM. HAIR CORTISOL CONCENTRATIONS WERE COMPARED WITHIN AND AMONG THE GROUPS USING NON-PARAMETRIC STATISTICAL TESTS. RESULTS: HAIR CORTISOL CONCENTRATIONS INCREASED ACROSS TRIMESTERS FOR ALL THREE GROUPS, BUT THIS INCREASE WAS DAMPENED IN WOMEN WITH ASTHMA (P = 0.03 FOR CONTROLS VS. ICS TREATED AND CONTROLS VS. NO ICS). ICS TREATED WOMEN TAKING MORE THAN FIVE DOSES PER WEEK HAD HAIR CORTISOL CONCENTRATIONS 47 % LOWER IN THIRD TRIMESTER THAN CONTROLS. LINEAR REGRESSION OF THE THIRD TRIMESTER HAIR CORTISOL RESULTS IDENTIFIED ASTHMA AS A SIGNIFICANT FACTOR WHEN COMPARING CONSISTENT ICS USE OR ASTHMA AS THE PREDICTOR (F(1, 25) = 9.7, P = 0.005, R(2) ADJ = 0.257). CONCLUSIONS: HAIR CORTISOL SUCCESSFULLY SHOWED THE EXPECTED CHANGE IN CORTISOL OVER THE COURSE OF PREGNANCY AND MAY BE A USEFUL BIOMARKER OF HPA AXIS FUNCTION IN PREGNANT WOMEN WITH ASTHMA. THE POTENTIAL IMPACT OF DECREASED MATERNAL CORTISOL IN WOMEN WITH ASTHMA ON PERINATAL OUTCOMES REMAINS TO BE DETERMINED.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
6  2734  37 EXPLORING THE RELATIONSHIP BETWEEN DNA METHYLATION AGE MEASURES AND PSYCHONEUROLOGICAL SYMPTOMS IN WOMEN WITH EARLY-STAGE BREAST CANCER. PURPOSE: THE EPIGENETIC CLOCK HAS BEEN ACKNOWLEDGED AS AN INDICATOR FOR MOLECULAR AGING, BUT FEW STUDIES HAVE EXAMINED POSSIBLE ASSOCIATIONS OF DNA METHYLATION (DNAM) AGE OR AGE ACCELERATION (AA) WITH SYMPTOM BURDEN IN INDIVIDUALS WHO ARE TREATED FOR CANCER. THIS STUDY EXPLORED THE ASSOCIATION OF DNAM AGE OR AA WITH PSYCHONEUROLOGICAL (PN) SYMPTOMS, INCLUDING COGNITIVE IMPAIRMENT, FATIGUE, SLEEP DISTURBANCES, PAIN, AND DEPRESSIVE SYMPTOMS, IN BREAST CANCER SURVIVORS OVER A 2-YEAR PERIOD. METHODS: WE MEASURED PN SYMPTOMS USING RELIABLE INSTRUMENTS AND DNAM LEVELS BY INFINIUM HUMANMETHYLATION450K BEADCHIP (N = 72). DNAM AGE WAS CALCULATED BY THE HORVATH, GRIM, AND HANNUM-BASED INTRINSIC AND EXTRINSIC AGE ESTIMATIONS. AA WAS DEFINED BY THE RESIDUAL REGRESSING ESTIMATED EPIGENETIC AGE ON CHRONOLOGICAL AGE. MIXED REGRESSION MODELS WERE FITTED FOR AA AND CHANGES IN AA TO STUDY THE ASSOCIATION OVER TIME. SEPARATE LINEAR REGRESSION MODELS AND A MIXED-EFFECTS MODEL WERE FITTED FOR AA AT EACH TIME POINT. RESULTS: HORVATH-AA, GRIM-AA, AND EXTRINSIC EPIGENETIC AA WERE SIGNIFICANTLY CHANGED OVER TIME, WHILE INTRINSIC EPIGENETIC AA DID NOT EXHIBIT ANY TEMPORAL CHANGES. INCREASED AA WAS ASSOCIATED WITH GREATER ANXIETY AND FATIGUE, AS WELL AS WORSE COGNITIVE MEMORY, ADJUSTING FOR RACE, BMI, INCOME, CHEMOTHERAPY, RADIATION THERAPY, AND CHRONOLOGICAL AGE. INCREASED DNAM AGE WAS ASSOCIATED WITH GREATER ANXIETY OVER 2 YEARS. CONCLUSION: OUR FINDINGS SUGGEST DNAM AGE AND AA MAY BE ASSOCIATED WITH PN SYMPTOMS OVER THE COURSE OF CANCER TREATMENT AND SURVIVORSHIP. SOME PN SYMPTOMS MAY BE AMENABLE TO PREVENTIVE INTERVENTIONS TARGETED TO EPIGENETIC CLOCKS THAT INFLUENCE AGING-ASSOCIATED PROCESSES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
7   509  36 ASSOCIATION OF NUTRACEUTICAL SUPPLEMENTS WITH LONGER TELOMERE LENGTH. TELOMERES ARE NUCLEOTIDE TANDEM REPEATS LOCATED AT THE TIP OF EUKARYOTIC CHROMOSOMES THAT MAINTAIN GENOMIC INTEGRITY. THE GRADUAL SHORTENING OF TELOMERES LEADS TO CELLULAR SENESCENCE AND APOPTOSIS, A KEY MECHANISM OF AGING AND AGE?RELATED CHRONIC DISEASES. EPIGENETIC FACTORS, SUCH AS NUTRITION, EXERCISE AND TOBACCO CAN AFFECT THE RATE AT WHICH TELOMERES SHORTEN AND CAN MODIFY THE RISK OF DEVELOPING CHRONIC DISEASES. IN THIS STUDY, WE EVALUATED THE EFFECTS OF A COMBINATION OF NUTRACEUTICAL SUPPLEMENTS (NS) ON TELOMERE LENGTH (TL) IN HEALTHY VOLUNTEERS WITH NO MEDICAL HISTORY OF ANY DISEASE. PARTICIPANTS (N=47) WERE SELECTED FROM HEALTHY OUTPATIENTS VISITING A PRIVATE CLINIC AND WERE DIVIDED INTO THE EXPERIMENTAL GROUP (N=16), THAT RECEIVED THE NS AND THE CONTROL GROUP (N=31). WE ESTIMATED THE LENGTH OF SINGLE TELOMERES IN METAPHASE SPREAD LEUKOCYTES, ISOLATED FROM PERIPHERAL BLOOD, USING QUANTITATIVE?FLUORESCENT IN SITU HYBRIDIZATION (Q?FISH) ANALYSIS. THE LENGTH OF THE WHOLE TELOMERE GENOME WAS SIGNIFICANTLY INCREASED (P<0.05) FOR THE MEAN, 1ST QUARTILE AND MEDIAN MEASUREMENTS IN THE EXPERIMENTAL GROUP. SIMILAR FINDINGS WERE OBSERVED FOR SHORT TL (20TH PERCENTILE) (P<0.05) FOR THE MEDIAN AND 3RD QUARTILE MEASUREMENTS IN THE NS GROUP, COMPARED TO THE CONTROL GROUP. THE BENEFICIAL EFFECTS OF THE SUPPLEMENTS ON THE LENGTH OF SHORT TELOMERES REMAINED SIGNIFICANT (P<0.05) FOLLOWING ADJUSTMENT FOR AGE AND SEX. TELOMERES WERE MODERATELY LONGER IN FEMALE PATIENTS COMPARED TO THE MALE PATIENTS. ON THE WHOLE, THE FINDINGS OF THIS STUDY SUGGEST THAT THE ADMINISTRATION OF NS MAY BE LINKED TO SUSTAINING THE TL.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8   524  37 ASSOCIATIONS OF BDNF GENOTYPE AND PROMOTER METHYLATION WITH ACUTE AND LONG-TERM STROKE OUTCOMES IN AN EAST ASIAN COHORT. BACKGROUND: BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) HAS BEEN SHOWN TO PLAY AN IMPORTANT ROLE IN POSTSTROKE RECOVERY. BDNF SECRETION IS INFLUENCED BY GENETIC AND EPIGENETIC PROFILES. THIS STUDY AIMED TO INVESTIGATE WHETHER BDNF VAL66MET POLYMORPHISM AND PROMOTER METHYLATION STATUS WERE ASSOCIATED WITH OUTCOMES AT TWO WEEKS AND ONE YEAR AFTER STROKE. METHODS AND FINDINGS: A TOTAL OF 286 PATIENTS WERE EVALUATED AT THE TIME OF ADMISSION AND TWO WEEKS AFTER STROKE, AND 222 (78%) WERE FOLLOWED ONE YEAR LATER IN ORDER TO EVALUATE CONSEQUENCES OF STROKE AT BOTH ACUTE AND CHRONIC STAGES. STROKE OUTCOMES WERE DICHOTOMISED INTO GOOD AND POOR BY THE MODIFIED RANKIN SCALE. STROKE SEVERITY (NATIONAL INSTITUTES OF HEALTH STROKE SCALE), PHYSICAL DISABILITY (BARTHEL INDEX), AND COGNITIVE FUNCTION (MINI-MENTAL STATE EXAMINATION) WERE MEASURED. ASSOCIATIONS OF BDNF GENOTYPE AND METHYLATION STATUS ON STROKE OUTCOMES AND ASSESSMENT SCALE SCORES WERE INVESTIGATED USING LOGISTIC REGRESSION, REPEATED MEASURES ANOVA AND PARTIAL CORRELATION TESTS. BDNF VAL66MET POLYMORPHISM WAS INDEPENDENTLY ASSOCIATED WITH POOR OUTCOME AT 2 WEEKS AND AT 1 YEAR, AND WITH WORSENING PHYSICAL DISABILITY AND COGNITIVE FUNCTION OVER THAT PERIOD. HIGHER BDNF PROMOTER METHYLATION STATUS WAS INDEPENDENTLY ASSOCIATED WITH WORSE OUTCOMES AT 1 YEAR, AND WITH THE WORSENING OF PHYSICAL DISABILITY AND COGNITIVE FUNCTION. NO SIGNIFICANT GENOTYPE-METHYLATION INTERACTIONS WERE FOUND. CONCLUSIONS: A ROLE FOR BDNF IN POSTSTROKE RECOVERY WAS SUPPORTED, AND CLINICAL UTILITY OF BDNF GENETIC AND EPIGENETIC PROFILE AS PROGNOSTIC BIOMARKERS AND A TARGET FOR DRUG DEVELOPMENT WAS SUGGESTED.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
9  1746  32 EARLY LIFE ADVERSITY, PUBERTAL TIMING, AND EPIGENETIC AGE ACCELERATION IN ADULTHOOD. BACKGROUND: GIVEN ASSOCIATIONS LINKING EARLY LIFE ADVERSITY, PUBERTAL TIMING, AND BIOLOGICAL AGING, WE EXAMINED THE DIRECT AND INDIRECT EFFECTS OF EARLY LIFE TRAUMA ON ADULT BIOLOGICAL AGING (VIA AGE OF MENARCHE). METHODS: PARTICIPANTS WERE PREMENOPAUSAL WOMEN (N = 183). PATH MODELS EVALUATED WHETHER EARLY LIFE TRAUMA PREDICTED EARLY PUBERTAL TIMING AND THEREBY, ADULT EPIGENETIC AGE ACCELERATION (INDEXED VIA FOUR EPIGENETIC CLOCKS: HORVATH DNAM AGE, HANNUM DNAM AGE, DNAM PHENOAGE, AND DNAM GRIMAGE). SECONDARY ANALYSES EXPLORED THE EFFECTS OF TYPE OF TRAUMA (ABUSE AND NEGLECT) AND ADULT CHRONIC STRESS STATUS (CAREGIVER OF CHILD WITH AUTISM AND NON-CAREGIVER). RESULTS: EARLY LIFE TRAUMA AND EARLIER AGE AT MENARCHE INDEPENDENTLY PREDICTED ACCELERATED AGING BASED ON ONE OF THE FOUR EPIGENETIC CLOCKS, DNAM GRIMAGE, THOUGH EARLY LIFE TRAUMA WAS NOT ASSOCIATED WITH AGE OF MENARCHE. CHILDHOOD ABUSE, BUT NOT NEGLECT, PREDICTED FASTER EPIGENETIC AGING; RESULTS DID NOT DIFFER BY CHRONIC STRESS STATUS. CONCLUSIONS: EARLY TRAUMA AND EARLY MENARCHE APPEAR TO EXERT INDEPENDENT EFFECTS ON DNAM GRIMAGE, WHICH HAS BEEN SHOWN TO BE THE STRONGEST EPIGENETIC PREDICTOR OF MORTALITY RISK. THIS STUDY IDENTIFIES A POTENTIAL CORRELATE OR DETERMINANT OF ACCELERATED EPIGENETIC AGING-MENARCHEAL AGE. FUTURE RESEARCH SHOULD ADDRESS THE LIMITATIONS OF THIS STUDY BY USING RACIALLY DIVERSE SAMPLES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
10  1159  42 CONTEXTUAL MODIFIERS OF HEALTHSPAN, LIFESPAN, AND EPIGENOME IN MICE UNDER CHRONIC SOCIAL STRESS. SUSTAINED LIFE STRESS AND LOW SOCIOECONOMIC STATUS ARE AMONG THE MAJOR CAUSES OF AGING-RELATED DISEASES AND DECREASED LIFE EXPECTANCY. EXPERIMENTAL RODENT MODELS CAN HELP TO IDENTIFY THE UNDERLYING MECHANISMS, YET VERY FEW STUDIES ADDRESS THE LONG-TERM CONSEQUENCES OF SOCIAL STRESS ON AGING. WE CONDUCTED A RANDOMIZED STUDY INVOLVING MORE THAN 300 MALE MICE OF COMMONLY USED LABORATORY STRAINS (C57BL/6J, CD1, AND SV129EV) CHOSEN FOR THE SPONTANEOUS AGGRESSION GRADIENT AND STRESS-VULNERABILITY. MICE WERE EXPOSED TO A LIFELONG CHRONIC PSYCHOSOCIAL STRESS PROTOCOL TO MODEL SOCIAL GRADIENTS IN AGING AND DISEASE VULNERABILITY. LOW SOCIAL RANK, INFERRED BASED ON A DISCRETIZED AGGRESSION INDEX, WAS FOUND TO NEGATIVELY IMPACT LIFESPAN IN OUR STUDY POPULATION. HOWEVER, SOCIAL RANK INTERACTED WITH GENETIC BACKGROUND IN THAT LOW-RANKING C57BL/6J, HIGH-RANKING SV129EV, AND MIDDLE-RANKING CD1 MICE HAD LOWER SURVIVAL, RESPECTIVELY, IMPLYING A COST OF MAINTAINING A GIVEN SOCIAL RANK THAT VARIES ACROSS STRAINS. MACHINE LEARNING LINEAR DISCRIMINANT ANALYSIS IDENTIFIED BASELINE FAT-FREE MASS AS THE MOST IMPORTANT PREDICTOR OF MOUSE GENETIC BACKGROUND AND SOCIAL RANK IN THE PRESENT DATASET. FINALLY, STRAIN AND SOCIAL RANK DIFFERENCES WERE SIGNIFICANTLY ASSOCIATED WITH EPIGENETIC CHANGES, MOST SIGNIFICANTLY IN SV129EV MICE AND IN HIGH-RANKING COMPARED TO LOWER RANKING SUBJECTS. OVERALL, WE IDENTIFIED GENETIC BACKGROUND AND SOCIAL RANK AS CRITICAL CONTEXTUAL MODIFIERS OF AGING AND LIFESPAN IN AN ETHOLOGICALLY RELEVANT RODENT MODEL OF SOCIAL STRESS, THEREBY PROVIDING A PRECLINICAL EXPERIMENTAL PARADIGM TO STUDY THE IMPACT OF SOCIAL DETERMINANTS OF HEALTH DISPARITIES AND ACCELERATED AGING.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
11  6894  25 [SOCIAL INEQUALITY AND MENTAL HEALTH]. SOCIAL INEQUALITY REFERS TO THE INEQUITABLE DISTRIBUTION OF SOCIAL PROSPERITY INCLUDING THE RESOURCE OF HEALTH. THE RELATIONSHIP BETWEEN SOCIAL INEQUALITY AND MENTAL HEALTH CAN BE ESTABLISHED BY MEANS OF INDICATORS OF SOCIAL INEQUALITY THROUGHOUT ALL AGE GROUPS IN GERMANY. THERE ARE SOCIAL GRADIENTS OF MENTAL HEALTH ON THE POPULATION LEVEL, I.E. THE LINEAR RELATIONSHIP BETWEEN SOCIAL CLASSES OR STATUS AND STATE OF HEALTH. FUNDAMENTAL DETERMINANTS OF HEALTH DISPARITY ARE CULTURAL, SOCIAL, POLITICAL, AND GEOGRAPHICAL CONDITIONS, WHICH INTERACT WITH THE GENETIC MAKE-UP AND EPIGENETIC PROCESSES. THESE DETERMINANTS ALSO INFLUENCE THE MANAGEMENT OF DEVELOPMENTAL TASKS DURING THE LIFE COURSE AND ARE OF UTMOST IMPORTANCE FOR THE DEVELOPMENT OF MENTAL DISORDERS. THE MALADAPTATION TO CHRONIC STRESS IS AT THE CORE OF HEALTH DISPARITY. INTERVENTIONS AT THE INDIVIDUAL BEHAVIORAL LEVEL SHOULD COMPRISE THE DEVELOPMENT OF STRESS MANAGEMENT AND COPING STRATEGIES.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
12  6416  40 THE SURVEY OF THE HEALTH OF WISCONSIN (SHOW) PROGRAM: AN INFRASTRUCTURE FOR ADVANCING POPULATION HEALTH SCIENCES. PURPOSE: THE SURVEY OF THE HEALTH OF WISCONSIN (SHOW) WAS ESTABLISHED IN 2008 BY THE UNIVERSITY OF WISCONSIN (UW) SCHOOL OF MEDICINE AND PUBLIC HEALTH (SMPH) WITH THE GOALS OF 1) PROVIDING A TIMELY AND ACCURATE PICTURE OF THE HEALTH OF THE STATE RESIDENTS; AND 2) SERVING AS AN AGILE RESOURCE INFRASTRUCTURE FOR ANCILLARY STUDIES. TODAY SHOW CONTINUES TO SERVE AS A VITAL POPULATION HEALTH RESEARCH INFRASTRUCTURE. PARTICIPANTS: SHOW CURRENTLY INCLUDES 5,846 ADULT AND 980 MINOR PARTICIPANTS RECRUITED BETWEEN 2008-2019 IN FOUR PRIMARY WAVES. WAVE I (2008-2013) INCLUDES ANNUAL STATEWIDE REPRESENTATIVE SAMPLES OF 3,380 ADULTS AGES 21 TO 74 YEARS. WAVE II (2014-2016) IS A TRIANNUAL STATEWIDE SAMPLE OF 1957 ADULTS (AGE >/=18 YEARS) AND 645 CHILDREN. WAVE III (2017) CONSISTS OF FOLLOW-UP OF 725 ADULTS FROM THE WAVE I AND BASELINE SURVEYS OF 222 CHILDREN IN SELECTED HOUSEHOLDS. WAVES II AND III INCLUDE STOOL SAMPLES COLLECTED AS PART OF AN ANCILLARY STUDY IN A SUBSET OF 784 INDIVIDUALS. WAVE IV CONSIST OF 517 ADULTS AND 113 CHILDREN RECRUITED FROM TRADITIONALLY UNDER-REPRESENTED POPULATIONS IN BIOMEDICAL RESEARCH INCLUDING AFRICAN AMERICANS AND HISPANICS IN MILWAUKEE COUNTY, WI. FINDINGS TO DATE: THE SHOW PROVIDES EXTENSIVE DATA TO EXAMINE THE INTERSECTIONALITY OF MULTIPLE SOCIAL DETERMINANTS AND POPULATION HEALTH. SHOW INCLUDES A LARGE BIOREPOSITORY AND EXTENSIVE HEALTH DATA COLLECTED IN A GEOGRAPHICALLY DIVERSE URBAN AND RURAL POPULATION. OVER 60 STUDIES HAVE BEEN PUBLISHED COVERING A BROAD RANGE OF TOPICS INCLUDING, URBAN AND RURAL DISPARITIES IN CARDIO-METABOLIC DISEASE AND CANCER, OBJECTIVE PHYSICAL ACTIVITY, SLEEP, GREEN-SPACE AND MENTAL HEALTH, TRANSCRIPTOMICS, THE GUT MICROBIOME, ANTIBIOTIC RESISTANCE, AIR POLLUTION, CONCENTRATED ANIMAL FEEDING OPERATIONS AND HEAVY METAL EXPOSURES. FUTURE PLANS: THE SHOW COHORT IS AVAILABLE FOR CONTINUED LONGITUDINAL FOLLOW-UP AND ANCILLARY STUDIES INCLUDING GENETIC, MULTI-OMIC AND TRANSLATIONAL ENVIRONMENTAL HEALTH, AGING, MICROBIOME AND COVID-19 RESEARCH. ARTICLE SUMMARY: STRENGTHS AND LIMITATIONS: THE SURVEY OF THE HEALTH OF WISCONSIN (SHOW) IS AN INFRASTRUCTURE TO ADVANCE POPULATION HEALTH SCIENCES INCLUDING BIOLOGICAL SAMPLE COLLECTION AND BROADER DATA ON INDIVIDUAL AND NEIGHBORHOOD SOCIAL AND ENVIRONMENTAL DETERMINANTS OF HEALTH.THE EXTENSIVE DATA FROM DIVERSE URBAN AND RURAL POPULATIONS OFFERS A UNIQUE STUDY SAMPLE TO COMPARE HOW SOCIO-ECONOMIC GRADIENTS SHAPE HEALTH OUTCOMES IN DIFFERENT CONTEXTS.THE OBJECTIVE HEALTH DATA SUPPORTS NOVEL INTERDISCIPLINARY RESEARCH INITIATIVES AND IS ESPECIALLY SUITED FOR RESEARCH IN CAUSES AND CONSEQUENCES OF ENVIRONMENTAL EXPOSURES (PHYSICAL, CHEMICAL, SOCIAL) ACROSS THE LIFE COURSE ON CARDIOMETABOLIC HEALTH, IMMUNITY, AND AGING RELATED CONDITIONS.THE EXTENSIVE BIOREPOSITORY SUPPORTS NOVEL OMICS RESEARCH INTO COMMON BIOLOGICAL MECHANISMS UNDERLYING NUMEROUS COMPLEX CHRONIC CONDITIONS INCLUDING INFLAMMATION, OXIDATIVE STRESS, METABOLOMICS, AND EPIGENETIC MODULATION.ANCILLARY STUDIES, SUCH AS THE WISCONSIN MICROBIOME STUDY, HAVE EXPANDED THE UTILITY OF THE STUDY TO EXAMINE HUMAN SUSCEPTIBILITY TO ENVIRONMENTAL EXPOSURES AND OPPORTUNITIES FOR INVESTIGATIONS OF THE ROLE OF MICROBIOME IN HEALTH AND DISEASE.LONG-STANDING PARTNERSHIPS AND RECENT PARTICIPATION AMONG TRADITIONALLY UNDER-REPRESENTED POPULATIONS IN BIOMEDICAL RESEARCH OFFER NUMEROUS OPPORTUNITIES TO SUPPORT COMMUNITY-DRIVEN HEALTH EQUITY WORK.NO BIOLOGICAL SAMPLES WERE COLLECTED AMONG CHILDREN.THE STATEWIDE SAMPLING FRAME MAY LIMIT GENERALIZABILITY TO OTHER REGIONS IN THE UNITED STATES.	2021	

13  5957  37 TELOMERE LENGTH AND EPIGENETIC AGE ACCELERATION IN ADOLESCENTS WITH ANXIETY DISORDERS. EVIDENCE ON THE RELATIONSHIP BETWEEN GENETICS AND MENTAL HEALTH ARE FLOURISHING. HOWEVER, FEW STUDIES ARE EVALUATING EARLY BIOMARKERS THAT MIGHT LINK GENES, ENVIRONMENT, AND PSYCHOPATHOLOGY. WE AIMED TO STUDY TELOMERE LENGTH (TL) AND EPIGENETIC AGE ACCELERATION (AA) IN A COHORT OF ADOLESCENTS WITH AND WITHOUT ANXIETY DISORDERS (N = 234). WE EVALUATED A REPRESENTATIVE SUBSAMPLE OF PARTICIPANTS AT BASELINE AND AFTER 5 YEARS (N = 76) AND CATEGORIZED THEM ACCORDING TO THEIR ANXIETY DISORDER DIAGNOSIS AT BOTH TIME POINTS: (1) CONTROL GROUP (NO ANXIETY DISORDER, N = 18), (2) VARIABLE GROUP (ANXIETY DISORDER IN ONE EVALUATION, N = 38), AND (3) PERSISTENT GROUP (ANXIETY DISORDER AT BOTH TIME POINTS, N = 20). WE ASSESSED RELATIVE MEAN TL BY REAL-TIME QUANTITATIVE PCR AND DNA METHYLATION BY INFINIUM HUMANMETHYLATION450 BEADCHIP. WE CALCULATED AA USING THE HORVATH AGE ESTIMATION ALGORITHM AND ANALYZED DIFFERENCES AMONG GROUPS USING GENERALIZED LINEAR MIXED MODELS. THE PERSISTENT GROUP OF ANXIETY DISORDER DID NOT CHANGE TL OVER TIME (P = 0.495). THE VARIABLE GROUP HAD HIGHER BASELINE TL (P = 0.003) BUT NO ACCELERATED TL EROSION IN COMPARISON TO THE NON-ANXIETY CONTROL GROUP (P = 0.053). FURTHERMORE, THERE WERE NO DIFFERENCES IN AA AMONG GROUPS OVER TIME. OUR FINDINGS SUGGEST THAT ADOLESCENTS WITH CHRONIC ANXIETY DID NOT CHANGE TELOMERE LENGTH OVER TIME, WHICH COULD BE RELATED TO A DELAY IN NEURONAL DEVELOPMENT IN THIS PERIOD OF LIFE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
14    67  35 A LONGITUDINAL STUDY OF THE ASSOCIATIONS OF BDNF GENOTYPE AND METHYLATION WITH POSTSTROKE ANXIETY. BACKGROUND: ALTHOUGH THE PRECISE ETIOLOGY OF POSTSTROKE ANXIETY (PSA) HAS YET TO BE FULLY ELUCIDATED, IT IS KNOWN THAT BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) IS IMPORTANT FOR NEURAL PLASTICITY AND LONG-TERM POTENTIATION, ASSOCIATED WITH THE PATHOPHYSIOLOGY OF ANXIETY. THE EXPRESSION OF BDNF IS REGULATED BY EPIGENETIC AND GENETIC PROFILES. THUS, WE INVESTIGATED THE ASSOCIATION BETWEEN BDNF METHYLATION STATUS AND PSA AT 2 WEEKS AND 1 YEAR AFTER STROKE WHILE ACCOUNTING FOR INTERACTIONS WITH THE BDNF VAL66MET POLYMORPHISM. METHODS: THE BASELINE SAMPLE COMPRISED 286 PATIENTS WHO WERE ASSESSED AT 2 WEEKS AFTER STROKE; OF THESE PATIENTS, 222 (78%) WERE FOLLOWED UP WITH AT 1 YEAR AFTER STROKE. THE PRESENCE OF PSA WAS DETERMINED USING THE ANXIETY SUBSCALE OF THE HOSPITAL ANXIETY AND DEPRESSION SCALE (HADS), AND THE EFFECTS OF BDNF METHYLATION STATUS AND POLYMORPHISMS ON PSA STATUS WERE ASSESSED WITH MULTIVARIATE LOGISTIC REGRESSION MODELS. RESULTS: THE PREVALENCE OF PSA WAS SLIGHTLY LOWER (27 [9.4%]) AT BASELINE, AND 35 (15.8%) PATIENTS WERE IDENTIFIED AS HAVING PSA AT THE 1-YEAR FOLLOW-UP. STROKE PATIENTS WITH A HIGHER AVERAGE METHYLATION STATUS WERE MORE LIKELY TO HAVE PSA AT 1 YEAR. THE BDNF VAL66MET POLYMORPHISM WAS NOT INDEPENDENTLY ASSOCIATED WITH PSA DURING EITHER THE ACUTE OR CHRONIC PHASE AFTER STROKE, BUT THERE WAS A SIGNIFICANT INTERACTIVE EFFECT BETWEEN BDNF METHYLATION AND GENOTYPE ON PSA AT 2 WEEKS. CONCLUSIONS: IN THIS STUDY, BDNF METHYLATION IN COMBINATION WITH THE MET/MET BDNF POLYMORPHISM (VAL66MET POLYMORPHISM) WAS ASSOCIATED WITH PSA. THESE FINDINGS MAY HELP IDENTIFY PATIENTS AT HIGHER RISK FOR PSA.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
15   502  44 ASSOCIATION OF ARSENIC EXPOSURE WITH WHOLE BLOOD DNA METHYLATION: AN EPIGENOME-WIDE STUDY OF BANGLADESHI ADULTS. BACKGROUND: ARSENIC EXPOSURE AFFECTS [FORMULA: SEE TEXT] PEOPLE WORLDWIDE, INCLUDING [FORMULA: SEE TEXT] IN BANGLADESH. ARSENIC EXPOSURE INCREASES THE RISK OF CANCER AND OTHER CHRONIC DISEASES, AND ONE POTENTIAL MECHANISM OF ARSENIC TOXICITY IS EPIGENETIC DYSREGULATION. OBJECTIVE: WE ASSESSED ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND GENOME-WIDE DNA METHYLATION MEASURED AT BASELINE AMONG 396 BANGLADESHI ADULTS PARTICIPATING IN THE HEALTH EFFECTS OF ARSENIC LONGITUDINAL STUDY (HEALS) WHO WERE EXPOSED BY DRINKING NATURALLY CONTAMINATED WELL WATER. METHODS: METHYLATION IN WHOLE BLOOD DNA WAS MEASURED AT [FORMULA: SEE TEXT] USING THE ILLUMINA INFINIUMMETHYLATIONEPIC (EPIC) ARRAY. TO ASSESS ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND CPG METHYLATION, WE USED LINEAR REGRESSION MODELS ADJUSTED FOR COVARIATES AND SURROGATE VARIABLES (SVS) (CAPTURING UNKNOWN TECHNICAL AND BIOLOGIC FACTORS). WE ATTEMPTED REPLICATION AND CONDUCTED A META-ANALYSIS USING AN INDEPENDENT DATASET OF [FORMULA: SEE TEXT] FROM 400 BANGLADESHI INDIVIDUALS WITH ARSENICAL SKIN LESIONS. RESULTS: WE IDENTIFIED 34 CPGS ASSOCIATED WITH [FORMULA: SEE TEXT] CREATININE-ADJUSTED URINARY ARSENIC [[FORMULA: SEE TEXT]]. SIXTEEN OF THESE CPGS ANNOTATED TO THE [FORMULA: SEE TEXT] ARRAY, AND 10 ASSOCIATIONS WERE REPLICATED ([FORMULA: SEE TEXT]). THE TOP TWO CPGS ANNOTATED UPSTREAM OF THE ABR GENE (CG01912040, CG10003262 ). ALL URINARY ARSENIC-ASSOCIATED CPGS WERE ALSO ASSOCIATED WITH ARSENIC CONCENTRATION MEASURED IN DRINKING WATER ([FORMULA: SEE TEXT]). META-ANALYSIS ([FORMULA: SEE TEXT] SAMPLES) IDENTIFIED 221 URINARY ARSENIC-ASSOCIATED CPGS ([FORMULA: SEE TEXT]). THE ARSENIC-ASSOCIATED CPGS FROM THE META-ANALYSIS WERE ENRICHED IN NON-CPG ISLANDS AND SHORES ([FORMULA: SEE TEXT]) AND DEPLETED IN PROMOTER REGIONS ([FORMULA: SEE TEXT]). AMONG THE ARSENIC-ASSOCIATED CPGS ([FORMULA: SEE TEXT]), WE OBSERVED SIGNIFICANT ENRICHMENT OF GENES ANNOTATING TO THE REACTIVE OXYGEN SPECIES PATHWAY, INFLAMMATORY RESPONSE, AND TUMOR NECROSIS FACTOR [FORMULA: SEE TEXT] ([FORMULA: SEE TEXT]) SIGNALING VIA NUCLEAR FACTOR KAPPA-B ([FORMULA: SEE TEXT]) HALLMARKS ([FORMULA: SEE TEXT]). CONCLUSIONS: THE NOVEL AND REPLICABLE ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND DNA METHYLATION AT SPECIFIC CPGS OBSERVED IN THIS WORK SUGGEST THAT EPIGENETIC ALTERATIONS SHOULD BE FURTHER INVESTIGATED AS POTENTIAL MEDIATORS IN ARSENIC TOXICITY AND AS BIOMARKERS OF EXPOSURE AND EFFECT IN EXPOSED POPULATIONS. HTTPS://DOI.ORG/10.1289/EHP3849.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
16   173  36 ACCELERATED AGING IN BIPOLAR DISORDERS: AN EXPLORATORY STUDY OF SIX EPIGENETIC CLOCKS. BIPOLAR DISORDER (BD) IS A CHRONIC AND SEVERE PSYCHIATRIC DISORDER ASSOCIATED WITH SIGNIFICANT MEDICAL MORBIDITY AND REDUCED LIFE EXPECTANCY. IN THIS STUDY, WE ASSESSED ACCELERATED EPIGENETIC AGING IN INDIVIDUALS WITH BD USING VARIOUS DNA METHYLATION (DNAM)-BASED MARKERS. FOR THIS PURPOSE, WE USED FIVE EPIGENETIC CLOCKS (HORVATH, HANNUM, EN, PHENOAGE, AND GRIMAGE) AND A DNAM-BASED TELOMERE LENGTH CLOCK (DNAMTL). DNAM PROFILES WERE OBTAINED USING INFINIUM METHYLATIONEPIC ARRAYS FROM WHOLE-BLOOD SAMPLES OF 184 INDIVIDUALS WITH BD. WE ALSO ESTIMATED BLOOD CELL COUNTS BASED ON DNAM LEVELS FOR ADJUSTMENT. SIGNIFICANT CORRELATIONS BETWEEN CHRONOLOGICAL AGE AND EACH EPIGENETIC AGE ESTIMATED USING THE SIX DIFFERENT CLOCKS WERE OBSERVED. FOLLOWING ADJUSTMENT FOR BLOOD CELL COUNTS, WE FOUND THAT THE SIX EPIGENETIC AGEACCELS (AGE ACCELERATIONS) WERE SIGNIFICANTLY ASSOCIATED WITH THE BODY MASS INDEX. GRIMAGE AGEACCEL WAS SIGNIFICANTLY ASSOCIATED WITH MALE SEX, SMOKING STATUS AND CHILDHOOD MALTREATMENT. DNAMTL AGEACCEL WAS SIGNIFICANTLY ASSOCIATED WITH SMOKING STATUS. OVERALL, THIS STUDY SHOWED THAT DISTINCT EPIGENETIC CLOCKS ARE SENSITIVE TO DIFFERENT ASPECTS OF AGING PROCESS IN BD. FURTHER INVESTIGATIONS WITH COMPREHENSIVE EPIGENETIC CLOCK ANALYSES AND LARGE SAMPLES ARE REQUIRED TO CONFIRM OUR FINDINGS OF POTENTIAL DETERMINANTS OF AN ACCELERATED EPIGENETIC AGING IN BD.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
17  5085  33 PILOT STUDY OF ABSOLUTE TELOMERE LENGTHS IN PRETERM INFANTS. BACKGROUND: ANNUALLY, APPROXIMATELY 15 MILLION BABIES ARE BORN PRETERM (<37 WEEKS GESTATIONAL AGE) GLOBALLY. IN THE NEONATAL INTENSIVE CARE UNIT (NICU) ENVIRONMENT, INFANTS ARE EXPOSED TO REPEATED STRESSFUL OR PAINFUL PROCEDURES AS PART OF ROUTINE LIFESAVING CARE. THESE PROCEDURES HAVE BEEN ASSOCIATED WITH EPIGENETIC ALTERATIONS THAT MAY LEAD TO AN INCREASED RISK OF NEURODEVELOPMENTAL DISORDERS. TELOMERE LENGTH HAS BEEN NEGATIVELY ASSOCIATED WITH ADVERSE LIFE EXPERIENCES IN STUDIES OF ADULTS. OBJECTIVES: THIS PILOT STUDY AIMED TO DESCRIBE TELOMERE LENGTH IN A SAMPLE OF PRETERM INFANTS AT NICU DISCHARGE AND EXAMINE ANY ASSOCIATIONS WITH PAIN, FEEDING METHOD, AND NEURODEVELOPMENT. METHODS: THIS DESCRIPTIVE PILOT STUDY SAMPLE INCLUDES BASELINE ABSOLUTE TELOMERE LENGTH (ATL) OF 36 PRETERM INFANTS IMMEDIATELY PRIOR TO DISCHARGE. QUANTITATIVE POLYMERASE CHAIN REACTION WAS USED TO DETERMINE ATL. INFANT DEMOGRAPHICS, PAIN/STRESS, TYPE OF FEEDING, ANTIBIOTIC USE, NEURODEVELOPMENT, AND BUCCAL SWAB DATA WERE COLLECTED. DESCRIPTIVE DATA ANALYSIS WAS USED TO DESCRIBE THE TELOMERE LENGTH USING GRAPHS. RESULTS: AMONG OUR PRETERM INFANT SAMPLES, THE MEAN ATL WAS FAR GREATER THAN THE AVERAGE ADULT TELOMERE LENGTH. ALTHOUGH NO SIGNIFICANT ASSOCIATIONS WERE FOUND BETWEEN ATL AND PAIN, FEEDING METHOD, AND NEURODEVELOPMENT, A TREND BETWEEN SEX WAS NOTED WHERE MALE TELOMERE LENGTHS WERE SHORTER THAN FEMALES AS THEY AGED. DISCUSSION: THIS IS ONE OF FEW STUDIES TO EVALUATE PRETERM INFANT TELOMERE LENGTH. ALTHOUGH OTHER RESEARCHERS HAVE USED RELATIVE TELOMERE LENGTH, WE USED THE MORE ACCURATE ATL. WE FOUND NONSIGNIFICANT SHORTER TELOMERE LENGTHS AMONG MALES. ADDITIONAL LARGE-SCALE, LONGITUDINAL STUDIES ARE NEEDED TO BETTER IDENTIFY THE PREDICTORS OF TELOMERE LENGTH AT THE TIME OF DISCHARGE FROM NICU.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
18  5728  29 SLEEP QUALITY AND METHYLATION STATUS OF SELECTED TUMOR SUPPRESSOR GENES AMONG NURSES AND MIDWIVES. CHRONIC SLEEP RESTRICTION MAY AFFECT METABOLISM, HORMONE SECRETION PATTERNS AND INFLAMMATORY RESPONSES. LIMITED REPORTS SUGGEST ALSO EPIGENETIC EFFECTS, SUCH AS CHANGES IN DNA METHYLATION PROFILES. THE STUDY AIMS TO ASSESS THE POTENTIAL ASSOCIATION BETWEEN POOR SLEEP QUALITY OR SLEEP DURATION AND THE LEVELS OF 5-METHYLCYTOSINE IN THE PROMOTER REGIONS OF SELECTED TUMOR SUPPRESSOR GENES. A CROSS-SECTIONAL STUDY WAS CONDUCTED ON 710 NURSES AND MIDWIVES AGED 40-60 YEARS. DATA FROM INTERVIEWS REGARDING SLEEP HABITS AND POTENTIAL CONFOUNDERS WERE USED. THE METHYLATION STATUS OF TUMOR SUPPRESSOR GENES WAS DETERMINED VIA QMSP REACTIONS USING DNA SAMPLES DERIVED FROM LEUCOCYTES. NO SIGNIFICANT FINDINGS WERE OBSERVED IN THE TOTAL STUDY POPULATION OR IN THE TWO SUBGROUPS OF WOMEN STRATIFIED BY THE CURRENT SYSTEM OF WORK. A BORDERLINE SIGNIFICANCE ASSOCIATION WAS OBSERVED BETWEEN A SHORTER DURATION OF SLEEP AND AN INCREASED METHYLATION LEVEL IN CDKN2A AMONG DAY WORKING NURSES AND MIDWIVES. FURTHER STUDIES ARE WARRANTED TO EXPLORE THIS UNDER-INVESTIGATED TOPIC.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
19  1960  37 EPIGENETIC AGING IN CHILDREN FROM A SMALL-SCALE FARMING SOCIETY IN THE CONGO BASIN: ASSOCIATIONS WITH CHILD GROWTH AND FAMILY CONFLICT. DEVELOPMENTAL ENVIRONMENTS INFLUENCE INDIVIDUALS' LONG-TERM HEALTH TRAJECTORIES, AND THERE IS INCREASING EMPHASIS ON UNDERSTANDING THE BIOLOGICAL PATHWAYS THROUGH WHICH THIS OCCURS. EPIGENETIC AGING EVALUATES DNA METHYLATION AT A SUITE OF DISTINCT CPG SITES IN THE GENOME, AND EPIGENETIC AGE ACCELERATION (EAA) IS LINKED TO HEIGHTENED CHRONIC MORBIDITY AND MORTALITY RISKS IN ADULTS. CONSEQUENTLY, EAA PROVIDES INSIGHTS ON TRAJECTORIES OF BIOLOGICAL AGING, WHICH EARLY LIFE EXPERIENCES MAY HELP SHAPE. HOWEVER, FEW STUDIES HAVE MEASURED CORRELATES OF CHILDREN'S EPIGENETIC AGING, ESPECIALLY OUTSIDE OF THE U.S. AND EUROPE. IN PARTICULAR, LITTLE IS KNOWN ABOUT HOW CHILDREN'S GROWTH AND DEVELOPMENT RELATE TO EAA IN ECOLOGIES IN WHICH ENERGETIC AND PATHOGENIC STRESSORS ARE COMMONPLACE. WE STUDIED EAA FROM DRIED BLOOD SPOTS AMONG BONDONGO CHILDREN (N = 54) RESIDING IN A SMALL-SCALE, FISHER-FARMER SOCIETY IN A REMOTE REGION OF THE REPUBLIC OF THE CONGO. HERE, INFECTIOUS DISEASE BURDENS AND THEIR RESULTANT ENERGY DEMANDS ARE HIGH. CHILDREN WHO WERE HEAVIER FOR HEIGHT OR TALLER FOR AGE, RESPECTIVELY, EXHIBITED GREATER EAA, INCLUDING INTRINSIC EAA, WHICH IS CONSIDERED TO MEASURE EAA INTERNAL TO CELLS. FURTHERMORE, WE FOUND THAT CHILDREN IN FAMILIES WITH MORE CONFLICT BETWEEN PARENTS HAD GREATER INTRINSIC EAA. THESE RESULTS SUGGEST THAT IN CONTEXTS IN WHICH LIMITED ENERGY MUST BE ALLOCATED TO COMPETING DEMANDS, MORE INVESTMENT IN GROWTH MAY COINCIDE WITH GREATER EAA, WHICH PARALLELS FINDINGS IN EUROPEAN CHILDREN WHO DO NOT FACE SIMILAR ENERGETIC CONSTRAINTS. OUR FINDINGS ALSO INDICATE THAT ASSOCIATIONS BETWEEN ADVERSE FAMILY ENVIRONMENTS AND GREATER INTRINSIC EAA WERE NONETHELESS OBSERVABLE BUT ONLY AFTER ADJUSTMENT FOR COVARIATES RELEVANT TO THE ENERGETICALLY AND IMMUNOLOGICALLY DEMANDING NATURE OF THE LOCAL ECOLOGY.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
20  5882  38 SYSTEMATIC REVIEW OF LUNG FUNCTION AND COPD WITH PERIPHERAL BLOOD DNA METHYLATION IN POPULATION BASED STUDIES. BACKGROUND: EPIGENETIC VARIATIONS IN PERIPHERAL BLOOD HAVE POTENTIAL AS BIOMARKERS FOR DISEASE. THIS SYSTEMATIC REVIEW ASSESSES THE ASSOCIATION OF LUNG FUNCTION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) WITH DNA METHYLATION PROFILES IN PERIPHERAL BLOOD FROM POPULATION-BASED STUDIES. METHODS: ONLINE DATABASES MEDLINE, EMBASE, AND WEB OF SCIENCE WERE SEARCHED. GOOGLE SCHOLAR WAS SEARCHED TO IDENTIFY GREY LITERATURE. AFTER REMOVING DUPLICATE ARTICLES, 1155 ARTICLES WERE INDEPENDENTLY SCREENED BY TWO INVESTIGATORS. PEER REVIEWED REPORTS ON POPULATION-BASED STUDIES THAT EXAMINED PERIPHERAL BLOOD DNA METHYLATION IN PARTICIPANTS WITH MEASURED LUNG FUNCTION (FEV1, FEV1/FVC RATIO) OR KNOWN COPD STATUS WERE SELECTED FOR FULL-TEXT REVIEW. SIX ARTICLES WERE SUITABLE FOR INCLUSION. INFORMATION REGARDING STUDY CHARACTERISTICS, DESIGNS, METHODOLOGIES AND CONCLUSIONS WAS EXTRACTED. A NARRATIVE SYNTHESIS WAS PERFORMED BASED ON PUBLISHED RESULTS. RESULTS: THREE OF THE SIX ARTICLES ASSESSED THE ASSOCIATION OF COPD WITH DNA METHYLATION, AND TWO OF THESE ALSO INCLUDED ASSOCIATIONS WITH LUNG FUNCTION. OVERALL, FIVE REPORTS EXAMINED THE ASSOCIATION OF LUNG FUNCTION WITH DNA METHYLATION PROFILES. FIVE OF THE SIX ARTICLES REPORTED 'SIGNIFICANT' RESULTS. HOWEVER, NO CONSISTENT CPG SITES WERE IDENTIFIED ACROSS STUDIES FOR COPD STATUS OR LUNG FUNCTION VALUES. CONCLUSIONS: DNA METHYLATION PATTERNS IN PERIPHERAL BLOOD FROM INDIVIDUALS WITH REDUCED LUNG FUNCTION OR COPD MAY BE DIFFERENT TO THOSE IN PEOPLE WITH NORMAL LUNG FUNCTION. HOWEVER, THIS SYSTEMATIC REVIEW DID NOT FIND ANY CONSISTENT ASSOCIATIONS OF LUNG FUNCTION OR COPD WITH DIFFERENTIALLY METHYLATED CPG SITES. LARGE STUDIES WITH A LONGITUDINAL DESIGN TO ADDRESS REVERSE CAUSALITY MAY PROVE A MORE FRUITFUL AREA OF RESEARCH. TRIAL REGISTRATION: PROSPERO 2016: CRD42016037352 .	2017