1  746 116 CANNABIS TERATOLOGY EXPLAINS CURRENT PATTERNS OF COLORADAN CONGENITAL DEFECTS: THE CONTRIBUTION OF INCREASED CANNABINOID EXPOSURE TO RISING TERATOLOGICAL TRENDS. RISING DELTA9-TETRAHYDROCANNABINOL CONCENTRATIONS IN MODERN CANNABIS INVITES INVESTIGATION OF THE TERATOLOGICAL IMPLICATIONS OF PRENATAL CANNABIS EXPOSURE. DATA FROM COLORADO RESPONDS TO CHILDREN WITH SPECIAL NEEDS (CRCSN), NATIONAL SURVEY OF DRUG USE AND HEALTH, AND DRUG ENFORCEMENT AGENCY WAS ANALYZED. SEVEN, 40, AND 2 DEFECTS WERE RISING, FLAT, AND FALLING, RESPECTIVELY, AND 10/12 SUMMARY INDICES ROSE. ATRIAL SEPTAL DEFECT, SPINA BIFIDA, MICROCEPHALUS, DOWN'S SYNDROME, VENTRICULAR SEPTAL DEFECT, AND PATENT DUCTUS ARTERIOSUS ROSE, AND ALONG WITH CENTRAL NERVOUS SYSTEM, CARDIOVASCULAR, GENITOURINARY, RESPIRATORY, CHROMOSOMAL, AND MUSCULOSKELETAL DEFECTS ROSE 5 TO 37 TIMES FASTER THAN THE BIRTH RATE (3.3%) TO GENERATE AN EXCESS OF 11 753 (22%) MAJOR ANOMALIES. CANNABIS WAS THE ONLY DRUG WHOSE USE GREW FROM 2000 TO 2014 WHILE PAIN RELIEVERS, COCAINE, ALCOHOL, AND TOBACCO DID NOT. THE CORRELATION OF CANNABIS USE WITH MAJOR DEFECTS IN 2014 (2019 DATASET) WAS R = .77, P = .0011. MULTIPLE CANNABINOIDS WERE LINKED WITH SUMMARY MEASURES OF CONGENITAL ANOMALIES AND WERE ROBUST TO MULTIVARIATE ADJUSTMENT.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
2 6911  14 [TWO GERMAN BIRTH COHORTS: GINIPLUS AND LISAPLUS]. NUMEROUS CHRONIC DISEASES IN CHILDHOOD AND ADULTHOOD HAVE THEIR ORIGINS IN PERINATAL LIFE AND ARE POTENTIALLY INFLUENCED BY TRANS-GENERATIONAL EPIGENETIC PROCESSES. THEREFORE, PROSPECTIVE BIRTH COHORTS CAN SUBSTANTIALLY CONTRIBUTE TO OUR KNOWLEDGE ABOUT THE ETIOLOGY OF DISEASES INCLUDING MODIFIABLE RISK FACTORS. THE TWO POPULATION-BASED GERMAN BIRTH COHORTS GINIPLUS AND LISAPLUS AIM TO DESCRIBE THE NATURAL COURSE OF CHRONIC DISEASES AND INTERMEDIATE PHENOTYPES IN CHILDHOOD AND ITS DETERMINANTS, AND TO IDENTIFY POTENTIAL GENETIC EFFECT MODIFICATIONS. IN THE MID-1990S, 5,991 (GINIPLUS) AND 3,097 (LISAPLUS) HEALTHY, TERM NEWBORNS WERE RECRUITED FOR LONG-TERM FOLLOW-UP IN FOUR REGIONS OF GERMANY. THE FOLLOW-UP RATE FOR THE FIRST 10 YEARS WAS ABOUT 55%. WE ANALYZED THE GROWTH AND DEVELOPMENT OF OVERWEIGHT, INFECTIONS AND ALLERGIC DISEASES, MENTAL AND ORAL HEALTH, METABOLIC AND INFLAMMATORY PARAMETERS AND THE ROLE OF POTENTIAL RISK FACTORS INCLUDING GENETICS. THE RESULTS OF THESE TWO BIRTH COHORTS SUBSTANTIALLY CONTRIBUTE TO THE CURRENT KNOWLEDGE ABOUT THE NATURAL COURSE OF THESE HEALTH PARAMETERS. THESE DATA WERE INCLUDED IN MANY INTERNATIONAL PROJECTS AND CONSORTIA FOR PURPOSES OF INTERNATIONAL COMPARISONS OF PREVALENCE AND CONSISTENCY OF FINDINGS, AND TO INCREASE THE POWER OF THE ANALYSES.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
3 2967  14 GENETIC AND EPIGENETIC REGULATION OF CATECHOL-O-METHYLTRANSFERASE IN RELATION TO INFLAMMATION IN CHRONIC FATIGUE SYNDROME AND FIBROMYALGIA. BACKGROUND: CATECHOL-O-METHYLTRANSFERASE (COMT) HAS BEEN SHOWN TO INFLUENCE CLINICAL PAIN, DESCENDING MODULATION, AND EXERCISE-INDUCED SYMPTOM WORSENING. COMT REGULATES NOCICEPTIVE PROCESSING AND INFLAMMATION, KEY PATHOPHYSIOLOGICAL FEATURES OF CHRONIC FATIGUE SYNDROME AND FIBROMYALGIA (CFS/FM). WE AIMED TO DETERMINE THE INTERACTIONS BETWEEN GENETIC AND EPIGENETIC MECHANISMS REGULATING COMT AND ITS INFLUENCE ON INFLAMMATORY MARKERS AND SYMPTOMS IN PATIENTS WITH CFS/FM. METHODS: A CASE-CONTROL STUDY WITH REPEATED-MEASURES DESIGN WAS USED TO REDUCE THE CHANCE OF FALSE POSITIVE AND INCREASE THE POWER OF OUR FINDINGS. FIFTY-FOUR PARTICIPANTS (28 PATIENTS WITH CFS/FM AND 26 CONTROLS) WERE ASSESSED TWICE WITHIN 4 DAYS. THE ASSESSMENT INCLUDED CLINICAL QUESTIONNAIRES, NEUROPHYSIOLOGICAL ASSESSMENT (PAIN THRESHOLDS, TEMPORAL SUMMATION, AND CONDITIONED PAIN MODULATION), AND BLOOD WITHDRAWAL IN ORDER TO ASSESS RS4818, RS4633, AND RS4680 COMT POLYMORPHISMS AND PERFORM HAPLOTYPE ESTIMATION, DNA METHYLATION IN THE COMT GENE (BOTH MB-COMT AND S-COMT PROMOTERS), AND CYTOKINE EXPRESSION (TNF-ALPHA, IFN-GAMMA, IL-6, AND TGF-BETA). RESULTS: COMT HAPLOTYPES WERE ASSOCIATED WITH DNA METHYLATION IN THE S-COMT PROMOTER, TGF-BETA EXPRESSION, AND SYMPTOMS. HOWEVER, THIS WAS NOT SPECIFIC FOR ONE CONDITION. SIGNIFICANT BETWEEN-GROUP DIFFERENCES WERE FOUND FOR INCREASED DNA METHYLATION IN THE MB-COMT PROMOTER AND DECREASED IFN-GAMMA EXPRESSION IN PATIENTS. DISCUSSION: OUR RESULTS ARE CONSISTENT WITH BASIC AND CLINICAL RESEARCH, PROVIDING INTERESTING INSIGHTS INTO GENETIC-EPIGENETIC REGULATORY MECHANISMS. MB-COMT DNA METHYLATION MIGHT BE AN INDEPENDENT FACTOR CONTRIBUTING TO THE PATHOPHYSIOLOGY OF CFS/FM. FURTHER RESEARCH ON DNA METHYLATION IN COMPLEX CONDITIONS SUCH AS CFS/FM IS WARRANTED. WE RECOMMEND FUTURE RESEARCH TO EMPLOY A REPEATED-MEASURE DESIGN TO CONTROL FOR BIOMARKERS VARIABILITY AND WITHIN-SUBJECT CHANGES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
4 3162  18 GREATER STRESS AND TRAUMA MEDIATE RACE-RELATED DIFFERENCES IN EPIGENETIC AGE BETWEEN BLACK AND WHITE YOUNG ADULTS IN A COMMUNITY SAMPLE. BLACK AMERICANS SUFFER LOWER LIFE EXPECTANCY AND SHOW SIGNS OF ACCELERATED AGING COMPARED TO OTHER AMERICANS. WHILE PREVIOUS STUDIES OBSERVE THESE DIFFERENCES IN CHILDREN AND POPULATIONS WITH CHRONIC ILLNESS, WHETHER THESE PATHOLOGIC PROCESSES EXIST OR HOW THESE PATHOLOGIC PROCESSES PROGRESS HAS YET TO BE EXPLORED PRIOR TO THE ONSET OF SIGNIFICANT CHRONIC ILLNESS, WITHIN A YOUNG ADULT POPULATION. THEREFORE, WE INVESTIGATED RACE-RELATED DIFFERENCES IN EPIGENETIC AGE IN A CROSS-SECTIONAL SAMPLE OF YOUNG PUTATIVELY HEALTHY ADULTS AND ASSESSED WHETHER LIFETIME STRESS AND/OR TRAUMA MEDIATE THOSE DIFFERENCES. BIOLOGICAL AND PSYCHOLOGICAL DATA WERE COLLECTED FROM SELF-REPORTED HEALTHY ADULT VOLUNTEERS WITHIN THE LOCAL NEW HAVEN AREA (399 VOLUNTEERS, 19.8% BLACK, MEAN AGE: 29.28). STRESS AND TRAUMA DATA WAS COLLECTED USING THE CUMULATIVE ADVERSITY INVENTORY (CAI) INTERVIEW, WHICH ASSESSED SPECIFIC TYPES OF STRESSORS, INCLUDING MAJOR LIFE EVENTS, TRAUMATIC EVENTS, WORK, FINANCIAL, RELATIONSHIP AND CHRONIC STRESSORS CUMULATIVELY OVER TIME. GRIMAGE ACCELERATION (GAA), DETERMINED FROM WHOLE BLOOD COLLECTED FROM PARTICIPANTS, MEASURED EPIGENETIC AGE. IN ORDER TO UNDERSTAND THE IMPACT OF STRESS AND TRAUMA ON GAA, EXPLORATORY MEDIATION ANALYSES WERE THEN USED. WE FOUND CUMULATIVE STRESSORS ACROSS ALL TYPES OF EVENTS (MEAN DIFFERENCE OF 6.9 P = 2.14E-4) AND GAA (BETA = 2.29 YEARS [1.57-3.01, P = 9.70E-10] FOR RACE, PARTIAL ETA(2) = 0.091, MODEL ADJUSTED R(2) = 0.242) WERE SIGNIFICANTLY GREATER IN BLACK COMPARED TO WHITE PARTICIPANTS. CRITICALLY, CAI TOTAL SCORE (PROPORTION MEDIATED: 0.185 [0.073-0.34, P = 6E-4]) SIGNIFICANTLY MEDIATED THE RELATIONSHIP BETWEEN RACE AND GAA. FURTHER ANALYSIS ATTRIBUTED THIS DIFFERENCE TO MORE TRAUMATIC EVENTS, PARTICULARLY ASSAULTIVE TRAUMAS AND DEATH OF LOVED ONES. OUR RESULTS SUGGEST THAT, PRIOR TO DEVELOPMENT OF SIGNIFICANT CHRONIC DISEASE, BLACK INDIVIDUALS HAVE INCREASED EPIGENETIC AGE COMPARED TO WHITE PARTICIPANTS AND THAT INCREASED CUMULATIVE STRESS AND TRAUMATIC EVENTS MAY CONTRIBUTE SIGNIFICANTLY TO THIS EPIGENETIC AGING DIFFERENCE.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
5 3860  13 ISOCHROMOSOME 13 IN A PATIENT WITH CHILDHOOD-ONSET SCHIZOPHRENIA, ADHD, AND MOTOR TIC DISORDER. BACKGROUND: A SMALL PERCENTAGE OF ALL CASES OF SCHIZOPHRENIA HAVE A CHILDHOOD ONSET. THE IMPACT ON THE INDIVIDUAL AND FAMILY CAN BE DEVASTATING. WE REPORT THE RESULTS OF GENETIC ANALYSES FROM A PATIENT WITH ONSET OF VISUAL HALLUCINATIONS AT 5 YEARS, AND A SUBSEQUENT DIAGNOSIS AT 9 YEARS OF SCHIZOPHRENIA, ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) WITH HYPERACTIVITY AND IMPULSIVITY, AND CHRONIC MOTOR TIC DISORDER. RESULTS: KARYOTYPIC ANALYSIS FOUND 45,XX,I(13)(Q10) IN ALL CELLS EXAMINED. ALPHA SATELLITE FISH OF ISOCHROMOSOME 13 REVEALED A LARGE UNSPLIT CENTROMERIC REGION, INTERPRETED AS TWO CENTROMERES SEPARATED BY MINIMAL OR UNDETECTABLE SHORT-ARM MATERIAL OR AS A SINGLE MONOCENTRIC CENTROMERE, INDICATING THAT THE ISOCHROMOSOME LIKELY FORMED POST-ZYGOTICALLY BY A SHORT ARM U-TYPE OR CENTROMERIC EXCHANGE. CHARACTERIZATION OF CHROMOSOME 13 SIMPLE TANDEM REPEATS AND AFFYMETRIX WHOLE-GENOME 6.0 SNP ARRAY HYBRIDIZATION FOUND HOMOZYGOSITY FOR ALL MARKERS, AND THE PRESENCE OF ONLY A SINGLE PATERNAL ALLELE IN INFORMATIVE MARKERS, CONSISTENT WITH AN ISODISOMIC ISOCHROMOSOME OF PATERNAL ORIGIN. ANALYSIS OF TWO CHROMOSOME 13 SCHIZOPHRENIA CANDIDATE GENES, D-AMINO ACID OXIDASE ACTIVATOR (DAOA) AND 5-HYDROXYTRYPTAMINE (SEROTONIN) RECEPTOR 2A (5-HTR2A), FAILED TO IDENTIFY NON-SYNONYMOUS CODING MUTATIONS BUT DID IDENTIFY HOMOZYGOUS RISK POLYMORPHISMS. CONCLUSIONS: WE REPORT A FEMALE PATIENT WITH CHILDHOOD-ONSET SCHIZOPHRENIA, ADHD, AND MOTOR TIC DISORDER ASSOCIATED WITH AN ISODISOMIC ISOCHROMOSOME 13 OF PATERNAL ORIGIN AND A 45,XX,I(13)(Q10Q10) KARYOTYPE. WE EXAMINED TWO POTENTIAL MECHANISMS TO EXPLAIN CHROMOSOME 13 INVOLVEMENT IN THE PATIENT'S PATHOLOGY, INCLUDING REDUCTION TO HOMOZYGOSITY OF A PATERNAL MUTATION AND REDUCTION TO HOMOZYGOSITY OF A PATERNAL COPY NUMBER VARIATION, BUT WERE UNABLE TO IDENTIFY ANY OVERTLY PATHOGENIC ABNORMALITY. FUTURE STUDIES MAY CONSIDER WHETHER EPIGENETIC MECHANISMS RESULTING FROM UNIPARENTAL DISOMY (UPD) AND THE LACK OF CHROMOSOME 13 MATERNAL ALLELES LEAD TO THE PATIENT'S FEATURES.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
6  181  11 ACCELERATED EPIGENETIC AGING MEDIATES THE ASSOCIATION BETWEEN VITAMIN D LEVELS AND KNEE PAIN IN COMMUNITY-DWELLING INDIVIDUALS. OBJECTIVES: TO EXAMINE THE RELATIONSHIP BETWEEN VITAMIN D STATUS AND PAIN INTENSITY AND DISABILITY IN INDIVIDUALS WITH AND WITHOUT KNEE PAIN, AND TO EXAMINE THE ROLE OF EPIGENETICS IN THIS RELATIONSHIP. DESIGN: CROSS-SECTIONAL ANALYSIS OF DATA FROM THE UPLOAD-2 STUDY (UNDERSTANDING PAIN AND LIMITATIONS IN OSTEOARTHRITIC DISEASE-2). PARTICIPANTS: 189 INDIVIDUALS AGED 45-65 YEARS AND OLDER. MEASUREMENTS: SERUM VITAMIN D LEVELS, PAIN RELATED INTERFERENCE AND CHARACTERISTIC PAIN INTENSITY MEASURES, AND THE EPIGENETIC CLOCK GRIMAGE DERIVED FROM BLOOD ANALYSES. RESULTS: LOWER VITAMIN D WAS ASSOCIATED WITH ADVANCED EPIGENETIC AGING (AGEACCELGRIM), GREATER PAIN AND DISABILITY AND THAT (AGEACCELGRIM) MEDIATED THE RELATIONSHIP BETWEEN VITAMIN D STATUS AND SELF-REPORTED PAIN (AB = -0.0799; CI [-0.1492, -0.0237]) AND DISABILITY (AB = -0.0669; CI [-0.1365, -0.0149]) OUTCOMES. CONCLUSION: THESE DATA SUPPORT THE NOTION THAT LIFESTYLE FACTORS SUCH AS NUTRITION STATUS PLAY A KEY ROLE IN AGING PROCESS, AS WELL AS THE DEVELOPMENT AND MAINTENANCE OF AGE-RELATED DISEASES SUCH AS PAIN. MODIFYING NUTRITION STATUS COULD HELP PROMOTE HEALTHY AGING AND REDUCE PAIN.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
7 6156  14 THE GENETIC INFLUENCE ON THE CORTICAL PROCESSING OF EXPERIMENTAL PAIN AND THE MODERATING EFFECT OF PAIN STATUS. BACKGROUND: RESEARCH SUGGESTS THAT THE COMT VAL(158)MET, BDNF VAL(66)MET AND OPRM1 A(118)G POLYMORPHISMS MODERATE THE EXPERIENCE OF PAIN. IN ORDER TO OBTAIN EXPERIMENTAL CONFIRMATION AND EXTENSION OF FINDINGS, CORTICAL PROCESSING OF EXPERIMENTALLY-INDUCED PAIN WAS USED. METHOD: A SAMPLE OF 78 INDIVIDUALS WITH CHRONIC LOW BACK PAIN COMPLAINTS AND 37 HEALTHY CONTROLS UNDERWENT EEG REGISTRATION. EVENT-RELATED POTENTIALS WERE MEASURED IN RESPONSE TO ELECTRICAL NOCICEPTIVE STIMULI AND MODERATION BY COMT VAL(158)MET, BDNF VAL(66)MET AND OPRM1 A(118)G POLYMORPHISMS WAS ASSESSED. RESULTS: GENETIC VARIATION DID NOT HAVE A DIRECT EFFECT ON CORTICAL PROCESSING OF EXPERIMENTAL PAIN. HOWEVER, GENETIC EFFECTS (COMT VAL(158)MET AND BDNF VAL(66)MET) ON EXPERIMENTAL PAIN WERE MODERATED BY THE PRESENCE OF CHRONIC PAIN. IN THE PRESENCE OF CHRONIC PAIN, THE COMT MET ALLELE AND THE BDNF MET ALLELE AUGMENTED CORTICAL PAIN PROCESSING, WHILST REDUCING PAIN PROCESSING IN PAIN-FREE CONTROLS. NO SIGNIFICANT EFFECTS WERE FOUND CONCERNING THE OPRM1 A(118)G POLYMORPHISM. CONCLUSIONS: THE CURRENT STUDY SUGGESTS THAT CHRONIC EXPERIENCE OF PAIN ENHANCES GENETIC SENSITIVITY TO EXPERIMENTALLY INDUCED MILDLY PAINFUL STIMULI, POSSIBLY THROUGH A PROCESS OF EPIGENETIC MODIFICATION.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
8 1138  13 COMPUTATIONAL METHODS FOR DETECTION OF DIFFERENTIALLY METHYLATED REGIONS USING KERNEL DISTANCE AND SCAN STATISTICS. MOTIVATION: RESEARCHERS IN GENOMICS ARE INCREASINGLY INTERESTED IN EPIGENETIC FACTORS SUCH AS DNA METHYLATION BECAUSE THEY PLAY AN IMPORTANT ROLE IN REGULATING GENE EXPRESSION WITHOUT CHANGES IN THE SEQUENCE OF DNA. ABNORMAL DNA METHYLATION IS ASSOCIATED WITH MANY HUMAN DISEASES. RESULTS: WE PROPOSE TWO DIFFERENT APPROACHES TO TEST FOR DIFFERENTIALLY METHYLATED REGIONS (DMRS) ASSOCIATED WITH COMPLEX TRAITS, WHILE ACCOUNTING FOR CORRELATIONS AMONG CPG SITES IN THE DMRS. THE FIRST APPROACH IS A NONPARAMETRIC METHOD USING A KERNEL DISTANCE STATISTIC AND THE SECOND ONE IS A LIKELIHOOD-BASED METHOD USING A BINOMIAL SPATIAL SCAN STATISTIC. THE KERNEL DISTANCE METHOD USES THE KERNEL FUNCTION, WHILE THE BINOMIAL SCAN STATISTIC APPROACH USES A MIXED-EFFECTS MODEL TO INCORPORATE CORRELATIONS AMONG CPG SITES. EXTENSIVE SIMULATIONS SHOW THAT BOTH APPROACHES HAVE EXCELLENT CONTROL OF TYPE I ERROR, AND BOTH HAVE REASONABLE STATISTICAL POWER. THE BINOMIAL SCAN STATISTIC APPROACH APPEARS TO HAVE HIGHER POWER, WHILE THE KERNEL DISTANCE METHOD IS COMPUTATIONALLY FASTER. THE PROPOSED METHODS ARE DEMONSTRATED USING DATA FROM A CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) STUDY.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
9 5464   8 RESILIENCE IN LONG-TERM VIRAL INFECTION: GENETIC DETERMINANTS AND INTERACTIONS. VIRUS-INDUCED NEUROLOGICAL SEQUELAE RESULTING FROM INFECTION BY THEILER'S MURINE ENCEPHALOMYELITIS VIRUS (TMEV) ARE USED FOR STUDYING HUMAN CONDITIONS RANGING FROM EPILEPTIC SEIZURES TO DEMYELINATING DISEASE. MOUSE STRAINS ARE TYPICALLY CONSIDERED SUSCEPTIBLE OR RESISTANT TO TMEV INFECTION BASED ON VIRAL PERSISTENCE AND EXTREME PHENOTYPES, SUCH AS DEMYELINATION. WE HAVE IDENTIFIED A BROADER SPECTRUM OF PHENOTYPIC OUTCOMES BY INFECTING STRAINS OF THE GENETICALLY DIVERSE COLLABORATIVE CROSS (CC) MOUSE RESOURCE. WE EVALUATED THE CHRONIC-INFECTION GENE EXPRESSION PROFILES OF HIPPOCAMPI AND THORACIC SPINAL CORDS FOR 19 CC STRAINS IN RELATION TO PHENOTYPIC SEVERITY AND TMEV PERSISTENCE. STRAINS WERE CLUSTERED BASED ON SIMILAR PHENOTYPIC PROFILES AND TMEV LEVELS AT 90 DAYS POST-INFECTION, AND WE CATEGORIZED DISTINCT TMEV RESPONSE PROFILES. THE THREE MOST COMMON PROFILES INCLUDED "RESISTANT" AND "SUSCEPTIBLE," AS BEFORE, AS WELL AS A "RESILIENT" TMEV RESPONSE GROUP WHICH EXPERIENCED BOTH TMEV PERSISTENCE AND MILD NEUROLOGICAL PHENOTYPES EVEN AT 90 DAYS POST-INFECTION. EACH PROFILE HAD A DISTINCT GENE EXPRESSION SIGNATURE, ALLOWING THE IDENTIFICATION OF PATHWAYS AND NETWORKS SPECIFIC TO EACH TMEV RESPONSE GROUP. CC FOUNDER HAPLOTYPES FOR GENES INVOLVED IN THESE PATHWAYS/NETWORKS REVEALED CANDIDATE RESPONSE-SPECIFIC ALLELES. THESE ALLELES DEMONSTRATED PLEIOTROPY AND EPIGENETIC (MIRNA) REGULATION IN LONG-TERM TMEV INFECTION, WITH PARTICULAR RELEVANCE FOR RESILIENT MOUSE STRAINS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
10 1671  17 DRD2 METHYLATION IS ASSOCIATED WITH EXECUTIVE CONTROL NETWORK CONNECTIVITY AND SEVERITY OF ALCOHOL PROBLEMS AMONG A SAMPLE OF POLYSUBSTANCE USERS. CHRONIC EXPOSURE TO ALCOHOL AND OTHER DRUGS OF ABUSE HAS BEEN ASSOCIATED WITH DELETERIOUS CONSEQUENCES, INCLUDING FUNCTIONAL CONNECTIVITY DEFICITS WITHIN NEURAL NETWORKS ASSOCIATED WITH EXECUTIVE CONTROL. ALTERED FUNCTIONAL CONNECTIVITY WITHIN THE EXECUTIVE CONTROL NETWORK (ECN) MIGHT UNDERLIE THE PROGRESSIVE INABILITY TO CONTROL CONSUMPTION OF ALCOHOL AND OTHER DRUGS AS SUBSTANCE USE DISORDERS PROGRESS. GENETIC AND EPIGENETIC FACTORS HAVE BEEN ASSOCIATED WITH SUBSTANCE USE DISORDERS (SUDS). FOR EXAMPLE, DOPAMINE RECEPTOR 2 (DRD2) FUNCTIONING HAS BEEN ASSOCIATED WITH ALCOHOL USE DISORDER (AUD) AND RELATED PHENOTYPES, INCLUDING CORRELATES OF EXECUTIVE FUNCTIONING. THE PRESENT STUDY AIMS TO EXPLORE THE RELATIONSHIP BETWEEN A CONTINUOUS MEASURE OF ALCOHOL-RELATED PROBLEMS, EPIGENETIC MARKERS (METHYLATION) WITHIN THE DRD2 GENE, AND FUNCTIONAL CONNECTIVITY WITHIN THE ECN AMONG A SAMPLE OF POLYSUBSTANCE USERS. A COMMUNITY SAMPLE OF 658 SUBJECTS, WHOSE CONSUMPTION OF ALCOHOL, NICOTINE, AND CANNABIS SPAN ACROSS A SPECTRUM OF QUANTITY AND FREQUENCY OF USE, WERE OBTAINED ACROSS PREVIOUS STUDIES IN POLYSUBSTANCE USING POPULATIONS. RESTING STATE FUNCTIONAL MAGNETIC RESONANCE IMAGING WAS ANALYZED TO IDENTIFY INTRINSIC CONNECTIVITY NETWORKS USING A PRIORI REGIONS OF INTEREST. METHYLATION MEASUREMENT OF FUNCTIONALLY RELEVANT SITES WITHIN THE DRD2 GENE WAS ACHIEVED VIA PYROSEQUENCING. REGRESSION-BASED MODELS, INCLUDING MEDIATION AND MODERATION MODELS, TESTED THE ASSOCIATION BETWEEN DRD2 METHYLATION, FUNCTIONAL CONNECTIVITY WITHIN INTRINSIC NEURAL NETWORKS (INCLUDING THE ECN), AND SEVERITY OF ALCOHOL PROBLEMS. RESULTS SUGGEST THAT AVERAGE DRD2 METHYLATION WAS NEGATIVELY ASSOCIATED WITH RIGHT ECN (RECN) AND LEFT ECN (LECN) CONNECTIVITY, BUT NOT ASSOCIATED WITH OTHER NETWORKS TESTED, AND DRD2 METHYLATION WAS SIGNIFICANTLY ASSOCIATED WITH ALCOHOL PROBLEMS SEVERITY. MEDIATION MODELS WERE NOT SUPPORTED, ALTHOUGH MODERATION MODELS SUGGESTED THAT CONNECTIVITY BETWEEN EDGES WITHIN THE RECN MODERATED THE RELATIONSHIP BETWEEN DRD2 METHYLATION AND AUD SEVERITY. RESULTS SUPPORT A THEORETICAL MODEL IN WHICH EPIGENETIC FACTORS ARE ASSOCIATED WITH NEUROBIOLOGICAL CORRELATES OF ALCOHOL CONSUMPTION AMONG A SAMPLE OF POLYSUBSTANCE USERS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                
11  686  17 BRAIN-SPECIFIC GENES CONTRIBUTE TO CHRONIC BUT NOT TO ACUTE BACK PAIN. INTRODUCTION: BACK PAIN IS THE LEADING CAUSE OF DISABILITY WORLDWIDE. ALTHOUGH MOST BACK PAIN CASES ARE ACUTE, 20% OF ACUTE PAIN PATIENTS EXPERIENCE CHRONIC BACK PAIN SYMPTOMS. IT IS UNCLEAR WHETHER ACUTE PAIN AND CHRONIC PAIN HAVE SIMILAR OR DISTINCT UNDERLYING GENETIC MECHANISMS. OBJECTIVES: TO CHARACTERIZE THE MOLECULAR AND CELLULAR PATHWAYS CONTRIBUTING TO ACUTE AND CHRONIC PAIN STATES. METHODS: CROSS-SECTIONAL OBSERVATIONAL GENOME-WIDE ASSOCIATION STUDY. RESULTS: A TOTAL OF 375,158 INDIVIDUALS FROM THE UK BIOBANK COHORT WERE INCLUDED IN THE DISCOVERY OF GENOME-WIDE ASSOCIATION STUDY. OF THOSE, 70,633 (19%) AND 32,209 (9%) INDIVIDUALS MET THE DEFINITION OF CHRONIC AND ACUTE BACK PAIN, RESPECTIVELY. A TOTAL OF 355 SINGLE NUCLEOTIDE POLYMORPHISM GROUPED INTO 13 LOCI REACHED THE GENOME-WIDE SIGNIFICANCE THRESHOLD (5X10(-8)) FOR CHRONIC BACK PAIN, BUT NONE FOR ACUTE. OF THESE, 7 LOCI WERE REPLICATED IN THE NORD-TRONDELAG HEALTH STUDY (HUNT) COHORT (19,760 CHRONIC LOW BACK PAIN CASES AND 28,674 PAIN-FREE CONTROLS). SINGLE NUCLEOTIDE POLYMORPHISM HERITABILITY WAS 4.6% (P=1.4X10(-78)) FOR CHRONIC BACK PAIN AND 0.81% (P=1.4X10-8) FOR ACUTE BACK PAIN. SIMILAR DIFFERENCES IN HERITABILITY ESTIMATES BETWEEN ACUTE AND CHRONIC BACK PAIN WERE FOUND IN THE HUNT COHORT: 3.4% (P=0.0011) AND 0.6% (P=0.851), RESPECTIVELY. PATHWAY ANALYSES, TISSUE-SPECIFIC HERITABILITY ENRICHMENT ANALYSES, AND EPIGENETIC CHARACTERIZATION SUGGEST A SUBSTANTIAL GENETIC CONTRIBUTION TO CHRONIC BUT NOT ACUTE BACK PAIN FROM THE LOCI PREDOMINANTLY EXPRESSED IN THE CENTRAL NERVOUS SYSTEM. CONCLUSION: CHRONIC BACK PAIN IS SUBSTANTIALLY MORE HERITABLE THAN ACUTE BACK PAIN. THIS HERITABILITY IS MOSTLY ATTRIBUTED TO GENES EXPRESSED IN THE BRAIN.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
12 2997  11 GENETIC VARIANTS IN DNMT1 AND THE RISK OF CARDIAC AUTONOMIC NEUROPATHY IN WOMEN WITH TYPE 1 DIABETES. AIMS/INTRODUCTION: EPIGENETICS PARTICIPATE IN THE PATHOGENESIS OF METABOLIC MEMORY, A SITUATION IN WHICH HYPERGLYCEMIA EXERTS PROLONGED DELETERIOUS EFFECTS EVEN AFTER ITS NORMALIZATION. WE TESTED THE HYPOTHESIS THAT GENETIC VARIANTS IN AN EPIGENETIC GENE COULD PREDISPOSE TO DIABETES COMPLICATIONS. MATERIAL AND METHODS: WE ASSESSED THE FREQUENCY OF FIVE SINGLE-NUCLEOTIDE POLYMORPHISMS IN THE GENE ENCODING DEOXYRIBONUCLEIC ACID METHYTRANSFERASE 1 (DNMT1; RS8112895, RS7254567, RS11085721, RS17291414 AND RS10854076), AND THEIR ASSOCIATIONS WITH DIABETIC KIDNEY DISEASE, RETINOPATHY, DISTAL POLYNEUROPATHY AND AUTONOMIC CARDIOVASCULAR NEUROPATHY IN 359 INDIVIDUALS WITH LONG-TERM TYPE 1 DIABETES. RESULTS: NONE OF THE SINGLE-NUCLEOTIDE POLYMORPHISMS STUDIED WAS SIGNIFICANTLY ASSOCIATED WITH THE PRESENCE OF CHRONIC COMPLICATIONS IN THE OVERALL POPULATION. HOWEVER, AFTER SEX STRATIFICATION, THE MINOR ALLELE C OF RS11085721 CONFERRED RISK FOR CARDIOVASCULAR NEUROPATHY IN WOMEN AFTER ADJUSTMENT FOR CONFOUNDING VARIABLES (ODDS RATIO 2.32; 95% CONFIDENCE INTERVAL 1.26-4.33; P = 0.006). CONCLUSIONS: THE FACT THAT HETEROZYGOUS MUTATIONS IN DNMT1 ARE ASSOCIATED WITH HEREDITARY SENSORY AUTONOMIC NEUROPATHY PROVIDES PLAUSIBILITY TO THE PRESENT FINDING. IF CONFIRMED IN INDEPENDENT SAMPLES, IT SUGGESTS THAT GENETIC VARIANTS IN EPIGENETIC GENES MIGHT PREDISPOSE TO MORE OR FEWER EPIGENETIC CHANGES IN THE FACE OF SIMILAR METABOLIC DERANGEMENTS TRIGGERED BY HYPERGLYCEMIA, CONSTITUTING THE "GENETICS OF EPIGENETICS" FOR MICROVASCULAR DIABETES COMPLICATIONS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
13 1782  17 EFFECT OF A 3-WEEK MULTIDISCIPLINARY BODY WEIGHT REDUCTION PROGRAM ON THE EPIGENETIC AGE ACCELERATION IN OBESE ADULTS. OBESITY AND AGING SHARE COMMON MOLECULAR AND CELLULAR MECHANISMS UNDERLYING THE PATHOPHYSIOLOGY OF CARDIOVASCULAR DISEASES (CVD), WHICH OCCUR FREQUENTLY IN BOTH CONDITIONS. DNA METHYLATION (DNAM) AGE, A BIOMARKER OF THE EPIGENETIC CLOCK, HAS BEEN PROPOSED AS A MORE ACCURATE PREDICTOR OF BIOLOGICAL AGING THAN CHRONOLOGICAL AGE. A POSITIVE DIFFERENCE BETWEEN AN INDIVIDUAL'S CHRONOLOGICAL AGE AND DNAM AGE IS REFERRED TO AS EPIGENETIC AGE ACCELERATION. THE OBJECTIVE OF THE PRESENT STUDY WAS TO EVALUATE THE EFFECTS OF A 3-WEEK IN-HOSPITAL BODY WEIGHT REDUCTION PROGRAM (BWRP) ON THE EPIGENETIC AGE ACCELERATION, AS WELL AS ON OTHER CARDIOMETABOLIC OUTCOMES, IN A COHORT OF 72 OBESE ADULTS (F/M: 43/29; (CHRONOLOGICAL) AGE: 51.5 +/- 14.5 YRS; BMI: 46.5 +/- 6.3 KG/M2). AT THE END OF THE BWRP, WHEN CONSIDERING THE ENTIRE POPULATION, BMI DECREASED, AND CHANGES IN BODY COMPOSITION WERE OBSERVED. THE BWRP ALSO PRODUCED BENEFICIAL METABOLIC EFFECTS AS DEMONSTRATED BY DECREASES IN GLUCOSE, INSULIN, HOMA-IR, TOTAL CHOLESTEROL, AND LDL CHOLESTEROL. A POST-BWRP IMPROVEMENT IN CARDIOVASCULAR FUNCTION WAS ALSO EVIDENT (I.E., DECREASES IN SYSTOLIC AND DIASTOLIC BLOOD PRESSURES AND HEART RATE). THE BWRP REDUCED SOME MARKERS OF SYSTEMIC INFLAMMATION, PARTICULARLY C-REACTIVE PROTEIN (CRP). FINALLY, VASCULAR AGE (VA) AND FRAMINGHAM RISK SCORE (FRS) WERE REDUCED AFTER THE BWRP. WHEN CONSIDERING THE ENTIRE POPULATION, DNAM AGE AND EPIGENETIC AGE ACCELERATION DID NOT DIFFER AFTER THE BWRP. HOWEVER, WHEN SUBDIVIDING THE POPULATION INTO TWO GROUPS BASED ON EACH SUBJECT'S EPIGENETIC AGE ACCELERATION (I.E., </=0 YRS OR >0 YRS), THE BWRP REDUCED THE EPIGENETIC AGE ACCELERATION ONLY IN OBESE SUBJECTS WITH A VALUE > 0 YRS (THUS BIOLOGICALLY OLDER THAN EXPECTED). AMONG ALL THE SINGLE DEMOGRAPHIC, LIFESTYLE, BIOCHEMICAL, AND CLINICAL CHARACTERISTICS INVESTIGATED, ONLY SOME MARKERS OF SYSTEMIC INFLAMMATION, SUCH AS CRP, WERE ASSOCIATED WITH THE EPIGENETIC AGE ACCELERATION. MOREOVER, CHRONOLOGICAL AGE WAS CORRELATED WITH DNAM AGE AND VA; FINALLY, THERE WAS A CORRELATION BETWEEN DNAM AGE AND VA. IN CONCLUSION, A 3-WEEK BWRP IS CAPABLE OF REDUCING THE EPIGENETIC AGE ACCELERATION IN OBESE ADULTS, BEING THE BWRP-INDUCED REJUVENATION EVIDENT IN SUBJECTS WITH AN EPIGENETIC AGE ACCELERATION > 0 YRS. BASED ON THE BWRP-INDUCED DECREASE IN CRP LEVELS, CHRONIC SYSTEMIC INFLAMMATION SEEMS TO PLAY A ROLE IN MEDIATING OBESITY-RELATED EPIGENETIC REMODELING AND BIOLOGICAL AGING. THUS, DUE TO THE STRONG ASSOCIATION OF CVD RISK WITH THE EPIGENETIC CLOCK AND MORBIDITY/MORTALITY, ANY EFFORT SHOULD BE MADE TO REDUCE THE LOW-GRADE CHRONIC INFLAMMATORY STATE IN OBESITY.	2022	

14 1355  12 DEVELOPMENT AND VALIDATION OF A SIMPLE GENERAL POPULATION LUNG CANCER RISK MODEL INCLUDING AHRR-METHYLATION. INTRODUCTION: SCREENING REDUCES LUNG CANCER MORTALITY OF HIGH-RISK POPULATIONS. CURRENTLY PROPOSED SCREENING ELIGIBILITY CRITERIA ONLY IDENTIFY HALF OF THOSE INDIVIDUALS, WHO LATER DEVELOP LUNG CANCER. THIS STUDY AIMED TO DEVELOP AND VALIDATE A SENSITIVE AND SIMPLE MODEL FOR PREDICTING 10-YEAR LUNG CANCER RISK. METHODS: USING THE 1991-94 EXAMINATION OF THE COPENHAGEN CITY HEART STUDY IN DENMARK, 6,820 FORMER OR CURRENT SMOKERS FROM THE GENERAL POPULATION WERE FOLLOWED FOR LUNG CANCER WITHIN 10 YEARS AFTER EXAMINATION. LOGISTIC REGRESSION OF BASELINE VARIABLES (AGE, SEX, EDUCATION, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, FAMILY HISTORY OF LUNG CANCER, SMOKING STATUS AND CUMULATIVE SMOKING, SECONDHAND SMOKING, OCCUPATIONAL EXPOSURES TO DUST AND FUME, BODY MASS INDEX, LUNG FUNCTION, PLASMA C-REACTIVE PROTEIN, AND AHRR(CG05575921) METHYLATION) IDENTIFIED THE BEST PREDICTIVE MODEL. THE MODEL WAS VALIDATED AMONG 3,740 FORMER OR CURRENT SMOKERS FROM THE 2001-03 EXAMINATION, ALSO FOLLOWED FOR 10 YEARS. A SIMPLE RISK CHART WAS DEVELOPED WITH POISSON REGRESSION. RESULTS: AGE, SEX, EDUCATION, SMOKING STATUS, CUMULATIVE SMOKING, AND AHRR(CG05575921) METHYLATION IDENTIFIED 65 OF 88 INDIVIDUALS WHO DEVELOPED LUNG CANCER IN THE VALIDATION COHORT. THE HIGHEST RISK GROUP, CONSISTING OF LESS EDUCATED MEN AGED >65 WITH CURRENT SMOKING STATUS AND CUMULATIVE SMOKING >20 PACK-YEARS, HAD ABSOLUTE 10-YEAR RISKS VARYING FROM 4% TO 16% BY AHRR(CG05575921) METHYLATION. CONCLUSION: A SIMPLE RISK CHART INCLUDING AGE, SEX, EDUCATION, SMOKING STATUS, CUMULATIVE SMOKING, AND AHRR(CG05575921) METHYLATION, IDENTIFIES INDIVIDUALS WITH 10-YEAR LUNG CANCER RISK FROM BELOW 1% TO 16%. INCLUDING AHRR(CG05575921) METHYLATION IN THE ELIGIBILITY CRITERIA FOR SCREENING IDENTIFIES SMOKERS WHO WOULD BENEFIT THE MOST FROM SCREENING.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
15 1847  17 EFFECTS OF VARIOUS ENVIRONMENTS ON EPIGENETIC SETTINGS AND CHROMOSOMAL DAMAGE. AIR POLLUTION IS A DOMINANT ENVIRONMENTAL EXPOSURE FACTOR WITH SIGNIFICANT HEALTH CONSEQUENCES. UNEXPECTEDLY, RESEARCH IN A HEAVILY POLLUTED REGION OF THE CZECH REPUBLIC, WITH TRADITIONAL HEAVY INDUSTRY, REVEALED REPEATEDLY THE LOWEST FREQUENCY OF MICRONUCLEI IN THE SEASON WITH THE HIGHEST CONCENTRATIONS OF AIR POLLUTANTS INCLUDING CARCINOGENIC BENZO[A]PYRENE (B[A]P). MOLECULAR FINDINGS HAVE BEEN COLLECTED FOR MORE THAN 10 YEARS FROM VARIOUS LOCATIONS OF THE CZECH REPUBLIC, WITH DIFFERING QUALITY OF AMBIENT AIR. PRELIMINARY CONCLUSIONS HAVE SUGGESTED ADAPTATION OF THE POPULATION FROM THE POLLUTED LOCALITY (OSTRAVA, MORAVIAN-SILESIAN REGION (MSR)) TO CHRONIC AIR POLLUTION EXPOSURE. IN THIS STUDY WE UTILIZE THE PREVIOUS FINDINGS AND, FOR THE FIRST TIME, INVESTIGATE MICRONUCLEI (MN) FREQUENCY BY TYPE: (I) CENTROMERE POSITIVE (CEN+) MN, REPRESENTING CHROMOSOMAL LOSSES, AND (II) CENTROMERE NEGATIVE (CEN-) MN REPRESENTING CHROMOSOMAL BREAKS. AS PREVIOUS RESULTS INDICATED DIFFERENCES BETWEEN POPULATIONS IN THE EXPRESSION OF XRCC5, A GENE INVOLVED IN THE NON-HOMOLOGOUS END-JOINING (NHEJ) REPAIR PATHWAY, POSSIBLE VARIATIONS IN EPIGENETIC SETTINGS IN THIS GENE WERE ALSO INVESTIGATED. THIS NEW RESEARCH WAS CONDUCTED IN TWO SEASONS IN THE GROUPS FROM TWO LOCALITIES WITH DIFFERENT AIR QUALITY LEVELS (OSTRAVA (OS) AND PRAGUE (PG)). THE OBTAINED NEW RESULTS SHOW SIGNIFICANTLY LOWER FREQUENCIES OF CHROMOSOMAL BREAKS IN THE OS SUBJECTS, RELATED TO THE HIGHEST AIR POLLUTION LEVELS (P < 0.001). IN CONTRAST, CHROMOSOMAL LOSSES WERE COMPARABLE BETWEEN BOTH GROUPS. IN ADDITION, SIGNIFICANTLY LOWER DNA METHYLATION WAS FOUND IN 14.3% OF THE ANALYZED CPG LOCI OF XRCC5 IN THE POPULATION FROM OS. IN CONCLUSION, THE EPIGENETIC ADAPTATION (HYPOMETHYLATION) IN XRCC5 INVOLVED IN THE NHEJ REPAIR PATHWAY IN THE POPULATION FROM THE POLLUTED REGION, WAS SUGGESTED AS A REASON FOR THE REDUCED LEVEL OF CHROMOSOMAL BREAKS. FURTHER RESEARCH IS NEEDED TO EXPLORE THE ADDITIONAL MECHANISMS, INCLUDING GENETIC ADAPTATION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
16  645  20 BIRTH DEFECTS IN GAZA: PREVALENCE, TYPES, FAMILIARITY AND CORRELATION WITH ENVIRONMENTAL FACTORS. THIS IS THE FIRST REPORT OF REGISTRATION AT BIRTH, AND OF INCIDENCE OF MAJOR STRUCTURAL BIRTH DEFECTS (BD) OBTAINED IN GAZA AT AL SHIFA HOSPITAL, WHERE 28% OF TOTAL BIRTHS IN GAZA STRIP OCCUR. DOCTORS REGISTERED 4,027 DELIVERIES, WITH A PROTOCOL COMPREHENSIVE OF CLINICAL, DEMOGRAPHIC, KIN AND ENVIRONMENTAL QUESTIONS. PREVALENCE OF BD IS 14/1,000, WITHOUT ASSOCIATION WITH INTERMARRIAGE OR GENDER OF THE CHILD. PREVALENCE OF LATE MISCARRIAGES AND STILL BIRTHS ARE RESPECTIVELY 23.3/1,000 AND 7.4/1,000, AND OF PREMATURE BIRTHS 19.6/1,000. COUPLES WITH A BD CHILD HAVE ABOUT 10 TIMES HIGHER FREQUENCY OF RECURRENCE OF A BD IN THEIR PROGENY THAN THOSE WITH NORMAL CHILDREN, BUT NONE OF THEIR 694 SIBLINGS AND ONLY 10/1,000 OF THEIR 1,423 PROGENY HAD BD, SIMILAR TO THE FREQUENCY IN GENERAL POPULATION. THESE DATA SUGGEST OCCURRENCE OF NOVEL GENETIC AND EPIGENETIC EVENTS IN DETERMINATION OF BD. CHILDREN WITH BD WERE BORN WITH HIGHER FREQUENCY (P < 0 001) IN FAMILIES WHERE ONE OR BOTH PARENTS WERE UNDER "WHITE PHOSPHORUS" ATTACK, THAT IN THE GENERAL POPULATION. BOMBING OF THE FAMILY HOME AND REMOVAL OF THE RUBBLE WERE ALSO FREQUENTLY REPORTED BY COUPLES WITH BD OCCURRENCE. THESE DATA SUGGESTS A CAUSATIVE/FAVORING ROLE OF ACUTE EXPOSURE OF PARENTS TO THE WEAPONS-ASSOCIATED CONTAMINANTS, AND/OR OF THEIR CHRONIC EXPOSURE FROM THEIR PERSISTENCE IN THE ENVIRONMENT ON THE EMBRYONIC DEVELOPMENT OF THEIR CHILDREN.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
17 3050  11 GENOME-WIDE ASSOCIATION ANALYSES FOR LUNG FUNCTION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE IDENTIFY NEW LOCI AND POTENTIAL DRUGGABLE TARGETS. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS CHARACTERIZED BY REDUCED LUNG FUNCTION AND IS THE THIRD LEADING CAUSE OF DEATH GLOBALLY. THROUGH GENOME-WIDE ASSOCIATION DISCOVERY IN 48,943 INDIVIDUALS, SELECTED FROM EXTREMES OF THE LUNG FUNCTION DISTRIBUTION IN UK BIOBANK, AND FOLLOW-UP IN 95,375 INDIVIDUALS, WE INCREASED THE YIELD OF INDEPENDENT SIGNALS FOR LUNG FUNCTION FROM 54 TO 97. A GENETIC RISK SCORE WAS ASSOCIATED WITH COPD SUSCEPTIBILITY (ODDS RATIO PER 1 S.D. OF THE RISK SCORE ( APPROXIMATELY 6 ALLELES) (95% CONFIDENCE INTERVAL) = 1.24 (1.20-1.27), P = 5.05 X 10(-49)), AND WE OBSERVED A 3.7-FOLD DIFFERENCE IN COPD RISK BETWEEN INDIVIDUALS IN THE HIGHEST AND LOWEST GENETIC RISK SCORE DECILES IN UK BIOBANK. THE 97 SIGNALS SHOW ENRICHMENT IN GENES FOR DEVELOPMENT, ELASTIC FIBERS AND EPIGENETIC REGULATION PATHWAYS. WE HIGHLIGHT TARGETS FOR DRUGS AND COMPOUNDS IN DEVELOPMENT FOR COPD AND ASTHMA (GENES IN THE INOSITOL PHOSPHATE METABOLISM PATHWAY AND CHRM3) AND DESCRIBE TARGETS FOR POTENTIAL DRUG REPOSITIONING FROM OTHER CLINICAL INDICATIONS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
18 5092  13 PLACENTAL EPIGENETIC MARKS RELATED TO GESTATIONAL WEIGHT GAIN REVEAL POTENTIAL GENES ASSOCIATED WITH OFFSPRING OBESITY PARAMETERS. OBJECTIVE: OFFSPRING EXPOSED TO GESTATIONAL OBESITY HAVE AN INCREASED RISK FOR CHRONIC DISEASES. INCREASING EVIDENCE SUGGESTS THAT EPIGENETICS MAY PLAY A MECHANISTIC ROLE IN METABOLIC PROGRAMMING. THIS STUDY AIMED TO IDENTIFY PLACENTAL DNA METHYLATION MARKS ASSOCIATED WITH GESTATIONAL WEIGHT GAIN (GWG) AND TO STUDY THEIR ASSOCIATION WITH OFFSPRING OBESITY PARAMETERS AT SCHOOL AGE. METHODS: A GLOBAL METHYLATION ARRAY WAS PERFORMED IN 24 PLACENTAS FROM MOTHERS WITH DIFFERENT DEGREES OF GWG (SCREENING SAMPLE). THE METHYLATION PERCENTAGE OF FOUR CYTOSINE-GUANINE (CPG) SITES AND THE RELATIVE EXPRESSION OF THE RESPECTIVE ANNOTATED GENES WERE STUDIED IN 90 ADDITIONAL PLACENTAS (VALIDATION SAMPLE). ASSOCIATIONS OF THESE EPIGENETIC MARKS WITH CLINICAL PARAMETERS IN THE OFFSPRING AT 6 YEARS OF AGE WERE EXAMINED. RESULTS: THE SCREENING ANALYSIS IDENTIFIED 104 CPG SITES (97 GENES) ASSOCIATED WITH GWG. THE VALIDATION ANALYSIS OF FOUR SELECTED CPG SITES (ANNOTATING FOR FRAT1, SNX5, AND KCNK3 GENES) SHOWED THAT THE UPREGULATION OF SNX5 METHYLATION, THE DOWNREGULATION OF FRAT1 METHYLATION, AND KCNK3 UNDEREXPRESSION ASSOCIATED WITH AN ADVERSE METABOLIC PHENOTYPE IN CHILDREN OF WOMEN WITH INCREASED GWG. CONCLUSIONS: THESE RESULTS SUGGEST THAT PLACENTAL REGULATION OF FRAT1, SNX5, AND KCNK3 RELATES TO OBESITY PARAMETERS IN OFFSPRING EXPOSED TO EXCESSIVE GWG AND THEREBY COULD CONDITION THE RISK FOR FUTURE METABOLIC DISORDERS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
19 5845  15 STUDY PROTOCOL FOR THE EPIGENETIC CHARACTERIZATION OF ANGOR PECTORIS ACCORDING TO THE AFFECTED CORONARY COMPARTMENT: GLOBAL AND COMPREHENSIVE ASSESSMENT OF THE RELATIONSHIP BETWEEN INVASIVE CORONARY PHYSIOLOGY AND MICRORNAS. BACKGROUND: MICRORNAS (MIRNAS) ARE NONCODING RNAS INVOLVED IN POST-TRANSCRIPTIONAL GENETIC REGULATION WITH A PROPOSED ROLE IN INTERCELLULAR COMMUNICATION. MIRNAS ARE CONSIDERED PROMISING BIOMARKERS IN ISCHEMIC HEART DISEASE. INVASIVE PHYSIOLOGICAL EVALUATION ALLOWS A PRECISE ASSESSMENT OF EACH AFFECTED CORONARY COMPARTMENT. ALTHOUGH SOME STUDIES HAVE ASSOCIATED THE EXPRESSION OF CIRCULATING MIRNAS WITH INVASIVE PHYSIOLOGICAL INDEXES, THEIR GLOBAL RELATIONSHIP WITH CORONARY COMPARTMENTS HAS NOT BEEN ASSESSED. HERE, WE WILL EVALUATE CIRCULATING MIRNAS PROFILES ACCORDING TO THE CORONARY PATTERN OF THE VASCULAR COMPARTMENT AFFECTATION. STUDY AND DESIGN: THIS IS AN INVESTIGATOR-INITIATED, MULTICENTRE, DESCRIPTIVE STUDY TO BE CONDUCTED AT THREE CENTRES IN SPAIN (NCT05374694). THE STUDY WILL INCLUDE ONE HUNDRED CONSECUTIVE PATIENTS OLDER THAN 18 YEARS WITH CHEST PAIN OF PRESUMED CORONARY CAUSE UNDERGOING INVASIVE PHYSIOLOGICAL EVALUATION, INCLUDING FRACTIONAL FLOW RESERVE (FFR) AND INDEX OF MICROVASCULAR RESISTANCE (IMR). PATIENTS WILL BE INITIALLY CLASSIFIED INTO FOUR GROUPS, ACCORDING TO FFR AND IMR: MACROVASCULAR AND MICROVASCULAR AFFECTATION (FFR</=0.80 / IMR>/=25), ISOLATED MACROVASCULAR AFFECTATION (FFR</=0.80 / IMR<25), ISOLATED MICROVASCULAR AFFECTATION (FFR>0.80 / IMR >/=25) AND NORMAL CORONARY INDEXES (FFR>0.80 / IMR<25). PATIENTS WITH ISOLATED MICROVASCULAR AFFECTATION OR NORMAL INDEXES WILL ALSO UNDERGO THE ACETYLCHOLINE TEST AND MAY BE RECLASSIFIED AS A FIFTH GROUP IN THE PRESENCE OF SPASM. A PANEL OF MIRNAS PREVIOUSLY ASSOCIATED WITH MOLECULAR MECHANISMS LINKED TO CHRONIC CORONARY SYNDROME WILL BE ANALYSED USING RT-QPCR. CONCLUSIONS: THE RESULTS OF THIS STUDY WILL IDENTIFY MIRNA PROFILES ASSOCIATED WITH PATTERNS OF CORONARY AFFECTATION AND WILL CONTRIBUTE TO A BETTER UNDERSTANDING OF THE MECHANISTIC PATHWAYS OF CORONARY PATHOLOGY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
20 3648  16 INCREASED RELATIVE ABUNDANCE OF RUMINOCCOCUS IS ASSOCIATED WITH REDUCED CARDIOVASCULAR RISK IN AN OBESE POPULATION. BACKGROUND: OBESITY IS A COMPLEX DISEASE WITH UNDERLYING GENETIC, ENVIRONMENTAL, PSYCHOLOGICAL, PHYSIOLOGICAL, MEDICAL, AND EPIGENETIC FACTORS. OBESITY CAN CAUSE VARIOUS DISORDERS, INCLUDING CARDIOVASCULAR DISEASES (CVDS), THAT ARE AMONG THE MOST PREVALENT CHRONIC CONDITIONS IN QATAR. RECENT STUDIES HAVE HIGHLIGHTED THE SIGNIFICANT ROLES OF THE GUT MICROBIOME IN IMPROVING THE PATHOLOGY OF VARIOUS DISEASES, INCLUDING OBESITY. THUS, IN THIS STUDY, WE AIMED TO INVESTIGATE THE EFFECTS OF DIETARY INTAKE AND GUT MICROBIAL COMPOSITION IN MODULATING THE RISK OF CVD DEVELOPMENT IN OBESE QATARI ADULTS. METHODS: WE ENROLLED 46 ADULT SUBJECTS (18-65 YEARS OF AGE) WHO WERE CLASSIFIED BASED ON THEIR CVD RISK SCORES, CALCULATED USING THE FRAMINGHAM FORMULA, INTO A CVD NO-RISK GROUP (SCORE OF <10%, N = 36) AND CVD RISK GROUP (SCORE OF >/=10%, N = 10). FOR EACH STUDY SUBJECT, WE MEASURED THE GUT MICROBIAL COMPOSITION WITH A 16S RDNA SEQUENCING METHOD THAT TARGETED THE V3-V4 REGION USING ILLUMINA MISEQ, AND THEIR NUTRITIONAL STATUS WAS RECORDED BASED ON 24-H DIETARY RECALL. DIETARY INTAKE, BACTERIAL TAXA SUMMARY, DIVERSITY INDEX, MICROBIAL MARKERS, PATHWAY ANALYSIS, AND NETWORK CORRELATION WERE DETERMINED FOR THE STUDY SUBJECTS. RESULTS: THE CVD RISK GROUP SHOWED A LOWER INTAKE OF VITAMIN D, REDUCED RELATIVE ABUNDANCE OF GENERA RUMINOCOCCUS AND BIFIDOBACTERIUM, NO CHANGE IN BACTERIAL DIVERSITY, AND HIGHER LEVELS OF TAURINE, HYPOTAURINE, AND LIPOIC ACID METABOLISM THAN THE CVD NO-RISK GROUP. BESIDES, THE RELATIVE ABUNDANCE OF GENUS RUMINOCOCCUS WAS POSITIVELY CORRELATED WITH THE INTAKE OF PROTEIN, MONOUNSATURATED FAT, VITAMIN A, AND VITAMIN D. CONCLUSION: TAKEN TOGETHER, OUR RESULTS SUGGEST THAT THE GENUS RUMINOCOCCUS COULD BE USED AS A MICROBIAL MARKER, AND ITS REDUCED RELATIVE ABUNDANCE COULD MEDIATE THE RISK OF CVDS IN THE OBESE QATARI POPULATION.	2022