1 6696 142 VARIATION IN GENOTYPE AND DNA METHYLATION PATTERNS BASED ON ALCOHOL USE AND CVD IN THE KOREAN GENOME AND EPIDEMIOLOGY STUDY (KOGES). ALCOHOL CONSUMPTION CAN INCREASE THE RISK OF CHRONIC DISEASES, SUCH AS MYOCARDIAL INFARCTION, CORONARY ARTERY DISEASE, HYPERLIPIDEMIA, AND HYPERTENSION. WE AIMED TO ASSESS THE ASSOCIATION BETWEEN GENOTYPE, DNA METHYLATION PATTERNS, ALCOHOL CONSUMPTION, AND CHRONIC DISEASES IN KOREAN POPULATION. WE ANALYZED 8840 SUBJECTS FOR GENOTYPES AND 446 FOR DNA METHYLATION AMONG THE 9351 SUBJECTS FROM THE KOREAN GENOME AND EPIDEMIOLOGY STUDY (KOGES). WE FURTHER DIVIDED BOTH GROUPS INTO TWO SUB-GROUPS ACCORDING TO THE PRESENCE/ABSENCE OF CHRONIC DISEASES. WE SELECTED GENES WHOSE METHYLATION VARIED SIGNIFICANTLY WITH ALCOHOL CONSUMPTION, AND VISUALIZED GENOTYPE AND DNA METHYLATION PATTERNS SPECIFIC TO EACH GROUP. GENOME-WIDE ASSOCIATION STUDY (GWAS) REVEALED SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) RS2074356 AND RS11066280 IN HECT DOMAIN E3 UBIQUITIN PROTEIN LIGASE 4 (HECTD4) TO BE SIGNIFICANTLY ASSOCIATED WITH ALCOHOL CONSUMPTION IN BOTH THE PRESENCE. THE RS12229654 GENOTYPE ALSO DISPLAYED SIGNIFICANTLY DIFFERENT PATTERNS WITH ALCOHOL CONSUMPTION. FURTHERMORE, WE RETRIEVED DIFFERENTIALLY METHYLATED REGIONS (DMRS) FROM FOUR GROUPS BASED ON SEX AND CHRONIC DISEASES AND COMPARED THEM BY DRINKING STATUS. IN GENOTYPE ANALYSIS, CARDIOVASCULAR DISEASES (CVDS) SHOWED A HIGHER PROPORTION IN DRINKER THAN IN NON-DRINKER, BUT NOT IN DMR ANALYSIS. ADDITIONALLY, WE ANALYZED THE ENRICHED GENE ONTOLOGY TERMS AND KYOTO GENE AND GENOME ENCYCLOPEDIA (KEGG) PATHWAYS AND VISUALIZED THE NETWORK, HEATMAP, AND UPSET PLOT. WE SHOW THAT THE PATTERN OF DNA METHYLATION ASSOCIATED WITH CVD IS STRONGLY INFLUENCED BY ALCOHOLISM. OVERALL, THIS STUDY IDENTIFIED GENETIC AND EPIGENETIC VARIANTS INFLUENCED BY ALCOHOL CONSUMPTION AND CHRONIC DISEASES. 2022 2 1607 35 DNA METHYLATION, COLON CANCER AND MEDITERRANEAN DIET: RESULTS FROM THE EPIC-ITALY COHORT. THE BIOLOGICAL MECHANISMS THROUGH WHICH ADHERENCE TO MEDITERRANEAN DIET (MD) PROTECTS AGAINST COLON CANCER (CC) ARE POORLY UNDERSTOOD. EVIDENCE SUGGESTS THAT CHRONIC INFLAMMATION MAY BE IMPLICATED IN THE PATHWAY. BOTH DIET AND CC ARE RELATED TO EPIGENETIC REGULATION. WE PERFORMED A NESTED CASE-CONTROL STUDY ON 161 PAIRS FROM THE ITALIAN COMPONENT OF THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION (EPIC) COHORT, IN WHICH WE LOOKED FOR THE METHYLATION SIGNALS IN DNA EXTRACTED FROM LEUCOCYTES ASSOCIATED WITH BOTH CC AND MD IN 995 CPGS LOCATED IN 48 INFLAMMATION GENES. THE DNA METHYLATION SIGNALS DETECTED IN THIS ANALYSIS WERE VALIDATED IN A SUBGROUP OF 47 CASE-CONTROL PAIRS AND FURTHER REPLICATED (WHERE VALIDATED) IN 95 NEW PAIRS BY MEANS OF PYROSEQUENCING. AMONG THE CPG SITES SELECTED A-PRIORI IN INFLAMMATION-RELATED GENES, SEVEN CPG SITES WERE FOUND TO BE ASSOCIATED WITH CC STATUS AND WITH MD, IN LINE WITH ITS PROTECTIVE EFFECT. ONLY TWO CPG SITES (CG17968347-SERPINE1 AND CG20674490-RUNX3) WERE VALIDATED USING BISULPHITE PYROSEQUENCING AND, AFTER REPLICATION, WE FOUND THAT DNA METHYLATION OF CG20674490-RUNX3 MAY BE A POTENTIAL MOLECULAR MEDIATOR EXPLAINING THE PROTECTIVE EFFECT OF MD ON CC ONSET. THE USE OF A 'MEET-IN-THE-MIDDLE' APPROACH TO IDENTIFY THE OVERLAP BETWEEN EXPOSURE AND PREDICTIVE MARKERS OF DISEASE IS INNOVATIVE IN STUDIES ON THE RELATIONSHIP BETWEEN DIET AND CANCER, IN WHICH EXPOSURE ASSESSMENT IS DIFFICULT AND THE MECHANISMS THROUGH WHICH THE NUTRIENTS EXERT THEIR PROTECTIVE EFFECT IS LARGELY UNKNOWN. 2019 3 6080 43 THE EFFECT OF DNA METHYLATION IN THE DEVELOPMENT AND PROGRESSION OF CHRONIC KIDNEY DISEASE IN THE GENERAL POPULATION: AN EPIGENOME-WIDE ASSOCIATION STUDY USING THE KOREAN GENOME AND EPIDEMIOLOGY STUDY DATABASE. BACKGROUND: ALTHOUGH KNOWLEDGE OF THE GENETIC FACTORS INFLUENCING KIDNEY DISEASE IS INCREASING, EPIGENETIC PROFILES, WHICH ARE ASSOCIATED WITH CHRONIC KIDNEY DISEASE (CKD), HAVE NOT BEEN FULLY ELUCIDATED. WE SOUGHT TO IDENTIFY THE DNA METHYLATION STATUS OF CPG SITES ASSOCIATED WITH REDUCED KIDNEY FUNCTION AND EXAMINE WHETHER THE IDENTIFIED CPG SITES ARE ASSOCIATED WITH CKD DEVELOPMENT. METHOD: WE ANALYZED DNA METHYLATION PATTERNS OF 440 PARTICIPANTS IN THE KOREAN GENOME AND EPIDEMIOLOGY STUDY (KOGES) WITH ESTIMATED GLOMERULAR FILTRATION RATES (EGFRS) >/= 60 ML/MIN/1.73 M(2) AT BASELINE. CKD DEVELOPMENT WAS DEFINED AS A DECREASE IN THE EGFR OF <60 AT ANY TIME DURING AN 8-YEAR FOLLOW-UP PERIOD ("CKD PREDICTION" ANALYSIS). IN ADDITION, AMONG THE 440 PARTICIPANTS, 49 PARTICIPANTS WHO UNDERWENT A SECOND METHYLATION PROFILING WERE ASSESSED FOR AN ASSOCIATION BETWEEN A DECLINE IN KIDNEY FUNCTION AND CHANGES IN THE DEGREE OF METHYLATION OF CPG SITES DURING THE 8 YEARS ("KIDNEY FUNCTION SLOPE" ANALYSIS). RESULTS: IN THE CKD PREDICTION ANALYSIS, METHYLATION PROFILES OF A TOTAL OF 403,129 CPG SITES WERE EVALUATED AT BASELINE IN 440 PARTICIPANTS, AND INCREASED AND DECREASED METHYLATION OF 268 AND 189 CPG SITES, RESPECTIVELY, WERE SIGNIFICANTLY CORRELATED WITH THE DEVELOPMENT OF CKD IN MULTIVARIABLE LOGISTIC REGRESSION. DURING KIDNEY FUNCTION SLOPE ANALYSIS USING FOLLOW-UP METHYLATION PROFILES OF 49 PARTICIPANTS, THE PERCENT METHYLATION CHANGES IN 913 CPG SITES SHOWED A LINEAR RELATIONSHIP WITH THE PERCENT CHANGE IN EGFR DURING 8 YEARS. DURING FUNCTIONAL ENRICHMENT ANALYSES FOR SIGNIFICANT CPG SITES FOUND IN THE CKD PREDICTION AND KIDNEY FUNCTION SLOPE ANALYSES, WE FOUND THAT THOSE CPG SITES REPRESENTED MAPK, PI3K/AKT, AND RAP1 PATHWAYS. IN ADDITION, THREE CPG SITES FROM THREE GENES, NPHS2, CHCHD4, AND AHR, WERE FOUND TO BE SIGNIFICANT IN THE CKD PREDICTION ANALYSIS AND RELATED TO A DECLINE IN KIDNEY FUNCTION. CONCLUSION: IT IS SUGGESTED THAT DNA METHYLATION ON SPECIFIC GENES IS ASSOCIATED WITH THE DEVELOPMENT OF CKD AND THE DETERIORATION OF KIDNEY FUNCTION. 2023 4 1590 32 DNA METHYLATION PROFILING IN HUMAN LUNG TISSUE IDENTIFIES GENES ASSOCIATED WITH COPD. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A SMOKING-RELATED DISEASE CHARACTERIZED BY GENETIC AND PHENOTYPIC HETEROGENEITY. ALTHOUGH ASSOCIATION STUDIES HAVE IDENTIFIED MULTIPLE GENOMIC REGIONS WITH REPLICATED ASSOCIATIONS TO COPD, GENETIC VARIATION ONLY PARTIALLY EXPLAINS THE SUSCEPTIBILITY TO LUNG DISEASE, AND SUGGESTS THE RELEVANCE OF EPIGENETIC INVESTIGATIONS. WE PERFORMED GENOME-WIDE DNA METHYLATION PROFILING IN HOMOGENIZED LUNG TISSUE SAMPLES FROM 46 CONTROL SUBJECTS WITH NORMAL LUNG FUNCTION AND 114 SUBJECTS WITH COPD, ALL FORMER SMOKERS. THE DIFFERENTIALLY METHYLATED LOCI WERE INTEGRATED WITH PREVIOUS GENOME-WIDE ASSOCIATION STUDY RESULTS. THE TOP 535 DIFFERENTIALLY METHYLATED SITES, FILTERED FOR A MINIMUM MEAN METHYLATION DIFFERENCE OF 5% BETWEEN CASES AND CONTROLS, WERE ENRICHED FOR CPG SHELVES AND SHORES. PATHWAY ANALYSIS REVEALED ENRICHMENT FOR TRANSCRIPTION FACTORS. THE TOP DIFFERENTIALLY METHYLATED SITES FROM THE INTERSECTION WITH PREVIOUS GWAS WERE IN CHRM1, GLT1D1, AND C10ORF11; SORTED BY GWAS P-VALUE, THE TOP SITES INCLUDED FRMD4A, THSD4, AND C10ORF11. EPIGENETIC ASSOCIATION STUDIES COMPLEMENT GENETIC ASSOCIATION STUDIES TO IDENTIFY GENES POTENTIALLY INVOLVED IN COPD PATHOGENESIS. ENRICHMENT FOR GENES IMPLICATED IN ASTHMA AND LUNG FUNCTION AND FOR TRANSCRIPTION FACTORS SUGGESTS THE POTENTIAL PATHOGENIC RELEVANCE OF GENES IDENTIFIED THROUGH DIFFERENTIAL METHYLATION AND THE INTERSECTION WITH A BROADER RANGE OF GWAS ASSOCIATIONS. 2016 5 4750 41 NOVEL REGIONAL AGE-ASSOCIATED DNA METHYLATION CHANGES WITHIN HUMAN COMMON DISEASE-ASSOCIATED LOCI. BACKGROUND: ADVANCING AGE PROGRESSIVELY IMPACTS ON RISK AND SEVERITY OF CHRONIC DISEASE. IT ALSO MODIFIES THE EPIGENOME, WITH CHANGES IN DNA METHYLATION, DUE TO BOTH RANDOM DRIFT AND VARIATION WITHIN SPECIFIC FUNCTIONAL LOCI. RESULTS: IN A DISCOVERY SET OF 2238 PERIPHERAL-BLOOD GENOME-WIDE DNA METHYLOMES AGED 19-82 YEARS, WE IDENTIFY 71 AGE-ASSOCIATED DIFFERENTIALLY METHYLATED REGIONS WITHIN THE LINKAGE DISEQUILIBRIUM BLOCKS OF THE SINGLE NUCLEOTIDE POLYMORPHISMS FROM THE NIH GENOME-WIDE ASSOCIATION STUDY CATALOGUE. THIS INCLUDED 52 NOVEL REGIONS, 29 WITHIN LOCI NOT COVERED BY 450 K OR 27 K ILLUMINA ARRAY, AND WITH ENRICHMENT FOR DNASE-I HYPERSENSITIVITY SITES ACROSS THE FULL RANGE OF TISSUES. THESE AGE-ASSOCIATED DIFFERENTIALLY METHYLATED REGIONS ALSO SHOW MARKED ENRICHMENT FOR ENHANCERS AND POISED PROMOTERS ACROSS MULTIPLE CELL TYPES. IN A REPLICATION SET OF 2084 DNA METHYLOMES, 95.7 % OF THE AGE-ASSOCIATED DIFFERENTIALLY METHYLATED REGIONS SHOWED THE SAME DIRECTION OF AGEING EFFECT, WITH 80.3 % AND 53.5 % REPLICATED TO P < 0.05 AND P < 1.85 X 10(-8), RESPECTIVELY. CONCLUSION: BY ANALYSING THE FUNCTIONALLY ENRICHED DISEASE AND TRAIT-ASSOCIATED REGIONS OF THE HUMAN GENOME, WE IDENTIFY NOVEL EPIGENETIC AGEING CHANGES, WHICH COULD BE USEFUL BIOMARKERS OR PROVIDE MECHANISTIC INSIGHTS INTO AGE-RELATED COMMON DISEASES. 2016 6 2921 38 GENE-SPECIFIC DIFFERENTIAL DNA METHYLATION AND CHRONIC ARSENIC EXPOSURE IN AN EPIGENOME-WIDE ASSOCIATION STUDY OF ADULTS IN BANGLADESH. BACKGROUND: INORGANIC ARSENIC IS ONE OF THE MOST COMMON NATURALLY OCCURRING CONTAMINANTS FOUND IN THE ENVIRONMENT. ARSENIC IS ASSOCIATED WITH A NUMBER OF HEALTH OUTCOMES, WITH EPIGENETIC MODIFICATION SUGGESTED AS A POTENTIAL MECHANISM OF TOXICITY. OBJECTIVE: AMONG A SAMPLE OF 400 ADULT PARTICIPANTS, WE EVALUATED THE ASSOCIATION BETWEEN ARSENIC EXPOSURE, AS MEASURED BY BLOOD AND URINARY TOTAL ARSENIC CONCENTRATIONS, AND EPIGENOME-WIDE WHITE BLOOD CELL DNA METHYLATION. METHODS: WE USED LINEAR REGRESSION MODELS TO EXAMINE THE ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND METHYLATION AT EACH CPG SITE, ADJUSTED FOR SEX, AGE, AND BATCH. DIFFERENTIALLY METHYLATED LOCI WERE SUBSEQUENTLY EXAMINED IN RELATION TO CORRESPONDING GENE EXPRESSION FOR FUNCTIONAL EVIDENCE OF GENE REGULATION. RESULTS: IN ADJUSTED ANALYSES, WE OBSERVED FOUR DIFFERENTIALLY METHYLATED CPG SITES WITH URINARY TOTAL ARSENIC CONCENTRATION AND THREE DIFFERENTIALLY METHYLATED CPG SITES WITH BLOOD ARSENIC CONCENTRATION, BASED ON THE BONFERRONI-CORRECTED SIGNIFICANCE THRESHOLD OF P < 1 X 10(-7). METHYLATION OF PLA2G2C (PROBE CG04605617) WAS THE MOST SIGNIFICANTLY ASSOCIATED LOCUS IN RELATION TO BOTH URINARY (P = 3.40 X 10(-11)) AND BLOOD ARSENIC CONCENTRATIONS (P = 1.48 X 10(-11)). THREE ADDITIONAL NOVEL METHYLATION LOCI-SQSTM1 (CG01225779), SLC4A4 (CG06121226), AND IGH (CG13651690)--WERE ALSO SIGNIFICANTLY ASSOCIATED WITH ARSENIC EXPOSURE. FURTHER, THERE WAS EVIDENCE OF METHYLATION-RELATED GENE REGULATION BASED ON GENE EXPRESSION FOR A SUBSET OF DIFFERENTIALLY METHYLATED LOCI. CONCLUSIONS: WE OBSERVED SIGNIFICANT ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND GENE-SPECIFIC DIFFERENTIAL WHITE BLOOD CELL DNA METHYLATION, SUGGESTING THAT EPIGENETIC MODIFICATIONS MAY BE AN IMPORTANT PATHWAY UNDERLYING ARSENIC TOXICITY. THE SPECIFIC DIFFERENTIALLY METHYLATED LOCI IDENTIFIED MAY INFORM POTENTIAL PATHWAYS FOR FUTURE INTERVENTIONS. 2015 7 2627 38 EPIGENOME-WIDE ASSOCIATION STUDY OF ADIPOSITY AND FUTURE RISK OF OBESITY-RELATED DISEASES. BACKGROUND: OBESITY IS AN ESTABLISHED RISK FACTOR FOR SEVERAL COMMON CHRONIC DISEASES SUCH AS BREAST AND COLORECTAL CANCER, METABOLIC AND CARDIOVASCULAR DISEASES; HOWEVER, THE BIOLOGICAL BASIS FOR THESE RELATIONSHIPS IS NOT FULLY UNDERSTOOD. TO EXPLORE THE ASSOCIATION OF OBESITY WITH THESE CONDITIONS, WE INVESTIGATED PERIPHERAL BLOOD LEUCOCYTE (PBL) DNA METHYLATION MARKERS FOR ADIPOSITY AND THEIR CONTRIBUTION TO RISK OF INCIDENT BREAST AND COLORECTAL CANCER AND MYOCARDIAL INFARCTION. METHODS: DNA METHYLATION PROFILES (ILLUMINA INFINIUM((R)) HUMANMETHYLATION450 BEADCHIP) FROM 1941 INDIVIDUALS FROM FOUR POPULATION-BASED EUROPEAN COHORTS WERE ANALYSED IN RELATION TO BODY MASS INDEX, WAIST CIRCUMFERENCE, WAIST-HIP AND WAIST-HEIGHT RATIO WITHIN A META-ANALYTICAL FRAMEWORK. IN A SUBSET OF THESE INDIVIDUALS, DATA ON GENOME-WIDE GENE EXPRESSION LEVEL, BIOMARKERS OF GLUCOSE AND LIPID METABOLISM WERE ALSO AVAILABLE. VALIDATION OF METHYLATION MARKERS ASSOCIATED WITH ALL ADIPOSITY MEASURES WAS PERFORMED IN 358 INDIVIDUALS. FINALLY, WE INVESTIGATED THE ASSOCIATION OF OBESITY-RELATED METHYLATION MARKS WITH BREAST, COLORECTAL CANCER AND MYOCARDIAL INFARCTION WITHIN RELEVANT SUBSETS OF THE DISCOVERY POPULATION. RESULTS: WE IDENTIFIED 40 CPG LOCI WITH METHYLATION LEVELS ASSOCIATED WITH AT LEAST ONE ADIPOSITY MEASURE. OF THESE, ONE CPG LOCUS (CG06500161) IN ABCG1 WAS ASSOCIATED WITH ALL FOUR ADIPOSITY MEASURES (P = 9.07X10(-)(8) TO 3.27X10(-18)) AND LOWER TRANSCRIPTIONAL ACTIVITY OF THE FULL-LENGTH ISOFORM OF ABCG1 (P = 6.00X10(-7)), HIGHER TRIGLYCERIDE LEVELS (P = 5.37X10(-)(9)) AND HIGHER TRIGLYCERIDES-TO-HDL CHOLESTEROL RATIO (P = 1.03X10(-10)). OF THE 40 INFORMATIVE AND OBESITY-RELATED CPG LOCI, TWO (IN IL2RB AND FGF18) WERE SIGNIFICANTLY ASSOCIATED WITH COLORECTAL CANCER (INVERSELY, P < 1.6X10(-3)) AND ONE INTERGENIC LOCUS ON CHROMOSOME 1 WAS INVERSELY ASSOCIATED WITH MYOCARDIAL INFARCTION (P < 1.25X10(-3)), INDEPENDENTLY OF OBESITY AND ESTABLISHED RISK FACTORS. CONCLUSION: OUR RESULTS SUGGEST THAT EPIGENETIC CHANGES, IN PARTICULAR ALTERED DNA METHYLATION PATTERNS, MAY BE AN INTERMEDIATE BIOMARKER AT THE INTERSECTION OF OBESITY AND OBESITY-RELATED DISEASES, AND COULD OFFER CLUES AS TO UNDERLYING BIOLOGICAL MECHANISMS. 2018 8 177 32 ACCELERATED EPIGENETIC AGING AND INFLAMMATORY/IMMUNOLOGICAL PROFILE (IPAGE) IN PATIENTS WITH CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS DEFINED BY A REDUCED ESTIMATED GLOMERULAR FILTRATION RATE (EGFR). THIS FAILURE CAN BE RELATED TO A PHENOTYPE OF ACCELERATED AGING. IN THIS WORK, WE CONSIDERED 76 PATIENTS WITH END-STAGE RENAL DISEASE (ESRD) AND 83 HEALTHY CONTROLS. WE CONCOMITANTLY EVALUATED FOR THE FIRST TIME TWO MEASURES THAT CAN BE INFORMATIVE OF THE RATE OF AGING, I.E., WHOLE BLOOD DNA METHYLATION USING THE ILLUMINA INFINIUM EPIC ARRAY AND PLASMA LEVELS OF A SELECTION OF INFLAMMATORY/IMMUNOLOGICAL PROTEINS USING MULTIPLEX IMMUNOASSAYS. FIRST OF ALL, WE DEMONSTRATED ACCELERATED AGING IN TERMS OF THE MOST COMMON EPIGENETIC AGE ESTIMATORS IN CKD PATIENTS. MOREOVER, WE DEVELOPED A NEW CLOCK/PREDICTOR OF AGE BASED ON THE INFLAMMATORY/IMMUNOLOGICAL PROFILE (IPAGE) AND IDENTIFIED THE INFLAMMATORY/IMMUNOLOGICAL BIOMARKERS DIFFERENTIALLY EXPRESSED BETWEEN CASES AND CONTROLS. IPAGE APPEARED TO BE MORE SENSITIVE THAN EPIGENETIC CLOCKS IN QUANTIFYING THE ACCELERATED AGING PHENOTYPE OF ESRD PATIENTS. INTERESTINGLY, WE DID NOT FIND ANY CORRELATION BETWEEN THE AGE ACCELERATION EVALUATED ACCORDING TO THE EPIGENETIC CLOCKS AND IPAGE IN EITHER THE ESRD GROUP OR THE CONTROL GROUP. ON THE WHOLE, OUR DATA SHOW A CONSISTENT ACCELERATED AGING PHENOTYPE IN ESRD PATIENTS, WHICH IS BETTER APPRECIATED BY QUANTIFYING THE UNDERLYING INFLAMMATORY PROCESSES (INFLAMMAGING) BY IPAGE THAN BY USING EPIGENETIC CLOCKS. 2022 9 57 38 A GENOME-WIDE ASSOCIATION STUDY OF QUANTITATIVE COMPUTED TOMOGRAPHIC EMPHYSEMA IN KOREAN POPULATIONS. EMPHYSEMA IS AN IMPORTANT FEATURE OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). GENETIC FACTORS LIKELY AFFECT EMPHYSEMA PATHOGENESIS, BUT THIS QUESTION HAS PREDOMINANTLY BEEN STUDIED IN THOSE OF EUROPEAN ANCESTRY. IN THIS STUDY, WE SOUGHT TO DETERMINE GENETIC COMPONENTS OF EMPHYSEMA SEVERITY AND CHARACTERIZE THE POTENTIAL FUNCTION OF THE ASSOCIATED LOCI IN KOREAN POPULATION. WE PERFORMED A GENOME-WIDE ASSOCIATION STUDY (GWAS) ON QUANTITATIVE EMPHYSEMA IN SUBJECTS WITH OR WITHOUT COPD FROM TWO KOREAN COPD COHORTS. WE INVESTIGATED THE FUNCTIONAL CONSEQUENCES OF THE LOCI USING EPIGENETIC ANNOTATION AND GENE EXPRESSION DATA. WE ALSO COMPARED OUR GWAS RESULTS WITH AN EPIGENOME-WIDE ASSOCIATION STUDY AND PREVIOUS DIFFERENTIAL GENE EXPRESSION ANALYSIS. IN TOTAL, 548 SUBJECTS (476 [86.9%] MALE) INCLUDING 514 COPD PATIENTS WERE EVALUATED. WE IDENTIFIED ONE GENOME-WIDE SIGNIFICANT SNP (P < 5.0 X 10(-8)), RS117084279, NEAR PIBF1. WE IDENTIFIED AN ADDITIONAL 57 SNPS (P < 5.0 X 10(-6)) ASSOCIATED WITH EMPHYSEMA IN ALL SUBJECTS, AND 106 SNPS (P < 5.0 X 10(-6)) IN COPD PATIENTS. OF THESE CANDIDATE SNPS, 2 (RS12459249, RS11667314) NEAR CYP2A6 WERE EXPRESSION QUANTITATIVE TRAIT LOCI IN LUNG TISSUE AND A SNP (RS11214944) NEAR NNMT WAS AN EXPRESSION QUANTITATIVE TRAIT LOCUS IN WHOLE BLOOD. OF NOTE, RS11214944 WAS IN LINKAGE DISEQUILIBRIUM WITH VARIANTS IN ENHANCER HISTONE MARKS IN LUNG TISSUE. SEVERAL GENES NEAR ADDITIONAL SNPS WERE IDENTIFIED IN OUR PREVIOUS EWAS STUDY WITH NOMINAL LEVEL OF SIGNIFICANCE. WE IDENTIFIED A NOVEL SNP ASSOCIATED WITH QUANTITATIVE EMPHYSEMA ON CT. INCLUDING THE NOVEL SNP, SEVERAL CANDIDATE SNPS IN OUR STUDY MAY PROVIDE CLUES TO THE GENETIC ETIOLOGY OF EMPHYSEMA IN ASIAN POPULATIONS. FURTHER RESEARCH AND VALIDATION OF THE LOCI WILL HELP DETERMINE THE GENETIC FACTORS FOR THE DEVELOPMENT OF EMPHYSEMA. 2021 10 1909 37 ENRICHMENT OF GENOMIC PATHWAYS BASED ON DIFFERENTIAL DNA METHYLATION PROFILES ASSOCIATED WITH CHRONIC MUSCULOSKELETAL PAIN IN OLDER ADULTS: AN EXPLORATORY STUDY. OUR STUDY AIMED TO IDENTIFY DIFFERENTIALLY METHYLATED CPGS/REGIONS AND THEIR ENRICHED GENOMIC PATHWAYS ASSOCIATED WITH UNDERLYING CHRONIC MUSCULOSKELETAL PAIN IN OLDER INDIVIDUALS. WE RECRUITED COGNITIVELY HEALTHY OLDER ADULTS WITH (N = 20) AND WITHOUT (N = 9) SELF-REPORTED MUSCULOSKELETAL PAIN AND COLLECTED DNA FROM PERIPHERAL BLOOD THAT WAS ANALYZED USING METHYLATIONEPIC ARRAYS. WE IDENTIFIED 31,739 HYPERMETHYLATED CPG AND 10,811 HYPOMETHYLATED CPG PROBES (PS 25) AND 104 NON-OBESE SUBJECTS WHO PARTICIPATED IN THE SOPI-STROKE STUDY IN KOREA. DNA METHYLATION WAS MEASURED USING BISULFITE AMPLICON SEQUENCING (BSAS). A GENERAL LINEAR MODEL OR RELATIVE CORRELATION WAS USED TO DETERMINE THE EFFECTS OF DNA METHYLATION ON OBESITY AND OBESE PHENOTYPES. NOTABLY, THE MEAN LEVEL OF DNA METHYLATION WAS SIGNIFICANTLY HIGHER IN THE OVERWEIGHT/OBESE GROUP THAN IN THE NON-OBESE GROUP (18.62% VS. 17.18%). FURTHER ANALYSES REVEALED SIGNIFICANT POSITIVE CORRELATIONS OF THE BMI, THE SERUM TOTAL CHOLESTEROL AND LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS WITH THE DNA METHYLATION LEVEL (P = 0.0493, P = 0.003, AND P = 0.0094, RESPECTIVELY). THE STUDY FINDINGS SUGGEST AN ASSOCIATION BETWEEN DNA METHYLATION AT THE TSPOAP1-AS1 PROMOTER AND OVERWEIGHT/OBESITY. ACCORDINGLY, METHYLATION IN THIS PROMOTER REGION MIGHT BE A POTENTIAL PREDICTOR OF OBESITY. 2020 20 1295 30 DECREASED GLOBAL DNA METHYLATION IN THE WHITE BLOOD CELLS OF HIGH FAT DIET FED VERVET MONKEYS (CHLOROCEBUS AETHIOPS). EPIGENETIC MECHANISMS ARE ASSOCIATED WITH THE DEVELOPMENT OF MANY CHRONIC DISEASES AND DUE TO THEIR REVERSIBLE NATURE OFFER A UNIQUE WINDOW OF OPPORTUNITY TO REVERSE THE DISEASE PHENOTYPE. THIS STUDY INVESTIGATED WHETHER GLOBAL DNA METHYLATION CORRELATES WITH DYSGLYCEMIA IN THE VERVET MONKEY (CHLOROCEBUS AETHIOPS). DIET-INDUCED CHANGES IN DNA METHYLATION WERE OBSERVED WHERE GLOBAL DNA METHYLATION WAS TWOFOLD LOWER IN MONKEYS FED A HIGH FAT DIET (N = 10) COMPARED TO MONKEYS FED A STANDARD DIET (N = 15). AN INVERSE CORRELATION WAS OBSERVED BETWEEN DNA METHYLATION, BLOOD GLUCOSE CONCENTRATIONS, BODYWEIGHT, AND AGE, ALTHOUGH THE ASSOCIATION WAS NOT STATISTICALLY SIGNIFICANT. CONSUMPTION OF A HIGH FAT DIET IS ASSOCIATED WITH THE DEVELOPMENT OF METABOLIC DISEASE; THUS, THESE RESULTS SUGGEST THE USE OF GLOBAL DNA METHYLATION AS A BIOMARKER TO ASSESS THE RISK FOR METABOLIC DISEASE. MOREOVER, THIS STUDY PROVIDES FURTHER SUPPORT FOR THE USE OF THE VERVET MONKEY AS A MODEL SYSTEM TO STUDY METABOLIC DISEASES SUCH AS TYPE 2 DIABETES. INTEGRATION OF ALTERED DNA METHYLATION PROFILES INTO PREDICTIVE MODELS COULD FACILITATE RISK STRATIFICATION AND ENABLE INTERVENTION STRATEGIES TO INHIBIT DISEASE PROGRESSION. SUCH INTERVENTIONS COULD INCLUDE LIFESTYLE MODIFICATIONS, FOR EXAMPLE, THE INCREASED CONSUMPTION OF FUNCTIONAL FOODS WITH THE CAPACITY TO MODULATE DNA METHYLATION, THUS POTENTIALLY REVERSING THE DISEASE PHENOTYPE AND PREVENTING DISEASE. 2014