{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001001922"],"host":["EGA"],"description":["EGA study EGAS00001001922"],"dataset_title":["BMI EWAS summary stats"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10<sup>-7</sup>, range P = 9.2 × 10<sup>-8</sup> to 6.0 × 10<sup>-46</sup>; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10<sup>-6</sup>, range P = 5.5 × 10<sup>-6</sup> to 6.1 × 10<sup>-35</sup>, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10<sup>-54</sup>). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity."],"pubmed_title":["Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity."],"pubmed_authors":["Wahl Simone S, Drong Alexander A, Lehne Benjamin B, Loh Marie M, Scott William R WR, Kunze Sonja S, Tsai Pei-Chien PC, Ried Janina S JS, Zhang Weihua W, Yang Youwen Y, Tan Sili S, Fiorito Giovanni G, Franke Lude L, Guarrera Simonetta S, Kasela Silva S, Kriebel Jennifer J, Richmond Rebecca C RC, Adamo Marco M, Afzal Uzma U, Ala-Korpela Mika M, Albetti Benedetta B, Ammerpohl Ole O, Apperley Jane F JF, Beekman Marian M, Bertazzi Pier Alberto PA, Black S Lucas SL, Blancher Christine C, Bonder Marc-Jan MJ, Brosch Mario M, Carstensen-Kirberg Maren M, de Craen Anton J M AJ, de Lusignan Simon S, Dehghan Abbas A, Elkalaawy Mohamed M, Fischer Krista K, Franco Oscar H OH, Gaunt Tom R TR, Hampe Jochen J, Hashemi Majid M, Isaacs Aaron A, Jenkinson Andrew A, Jha Sujeet S, Kato Norihiro N, Krogh Vittorio V, Laffan Michael M, Meisinger Christa C, Meitinger Thomas T, Mok Zuan Yu ZY, Motta Valeria V, Ng Hong Kiat HK, Nikolakopoulou Zacharoula Z, Nteliopoulos Georgios G, Panico Salvatore S, Pervjakova Natalia N, Prokisch Holger H, Rathmann Wolfgang W, Roden Michael M, Rota Federica F, Rozario Michelle Ann MA, Sandling Johanna K JK, Schafmayer Clemens C, Schramm Katharina K, Siebert Reiner R, Slagboom P Eline PE, Soininen Pasi P, Stolk Lisette L, Strauch Konstantin K, Tai E-Shyong ES, Tarantini Letizia L, Thorand Barbara B, Tigchelaar Ettje F EF, Tumino Rosario R, Uitterlinden Andre G AG, van Duijn Cornelia C, van Meurs Joyce B J JB, Vineis Paolo P, Wickremasinghe Ananda Rajitha AR, Wijmenga Cisca C, Yang Tsun-Po TP, Yuan Wei W, Zhernakova Alexandra A, Batterham Rachel L RL, Smith George Davey GD, Deloukas Panos P, Heijmans Bastiaan T BT, Herder Christian C, Hofman Albert A, Lindgren Cecilia M CM, Milani Lili L, van der Harst Pim P, Peters Annette A, Illig Thomas T, Relton Caroline L CL, Waldenberger Melanie M, Järvelin Marjo-Riitta MR, Bollati Valentina V, Soong Richie R, Spector Tim D TD, Scott James J, McCarthy Mark I MI, Elliott Paul P, Bell Jordana T JT, Matullo Giuseppe G, Gieger Christian C, Kooner Jaspal S JS, Grallert Harald H, Chambers John C JC"],"name_synonyms":["Obesity, Obese, unspecified, obesity., DNA methylation maintenance, Obesity NOS, Obesity [Ambiguous], Obese (finding), obesity disease, Adiposity, DNA, OBESITY NOS, DNA Methylations, Overweight and obesity, DNA methylation, Methylations, Methylation, obesity disorder, Obesity (disorder), Adiposis"],"description_synonyms":["Modb1, MGC130048, Other diseases of pericardium (disorder), Materials, Cardiovascular disease, single-organism developmental process, Other pericardial disease NOS (disorder), postnatal development, Other heart disease NOS (disorder), Cardiovascular disorder, A4, PAPILLARY MUSCLE DIS NEC, growth and development, DNA Methylations, Risk Factor Score, Cardiac Event, [X]Other specified diseases of pericardium (disorder), Adiposis, prevention, Relative, Obese, unspecified, Risk Factors, Disease of cardiovascular system (disorder), Body Mass, Associations, Other heart disease NOS, CVD, Leprb, prevention and control, Correlates, DM - Diabetes mellitus, gamma sarcoglycan, Cardiovascular Diseases, Adiposis., DNA methylation maintenance, Gene Expressions, Moods, [X]Other forms of heart disease (disorder), Tissue, Other ill-defined heart disease (disorder), Other diseases of endocardium, DNA methylation, circulatory system disease, DNA Methylomes, Social, genetic, preventive measures, Diabetes mellitus, Disorder of cardiovascular system, Health Correlates, Quetelet, gamma-sarcoglycan, Event, db, Circulatory system disease NOS (disorder), preventive therapy, wide/broad, DM, Index, Methylomes, SG-gamma, familial, Disorder of circulatory system, lipoprotein metabolism, results, disease of subdivision of hemolymphoid system, OB-RGRP, single-organism transport, Quetelet's Index, Lipid, Relative Risks, Obesity [Ambiguous], Obese (finding), Adverse Cardiac Event, Score, Genetic Materials, OBESITY, sarcoglycan, NOS, Other pericardial disease NOS, regulator, Methylome, Genetic Material, CIRCULATORY DISEASE NOS, CARDIOVASC DIS, Factors, Social Risk Factors, Risk, Adverse Cardiac Events, Disorder of the circulatory system, Adiposity, [X]Other ill-defined heart diseases (disorder), OBESITY NOS, gamma (35kDa dystrophin-associated glycoprotein), Obr, Diabetes NOS, Phenotypes, Social Risk, wide, Health, DMDA, Material, 35kD dystrophin-associated glycoprotein, ILL-DEFINED HRT DIS NEC, Cistron, inherited genetic, DNA, obl, Disease affecting entire cardiovascular system, Methylation, DNA Methylome, Cardiovascular Disorders, lipids, ASCVD, Cardiovascular system disease, Genetic Locus, SGCG_HUMAN, Other heart disease (disorder), obesity disease, Gene, Other diseases of pericardium, broad, Other disorders of papillary muscle, Adverse, TYPE, unspecified (disorder), Obesity, DAGA4, Disorder of cardiovascular system (disorder), [X]Cardiovascular disease, Cardiac, 35DAG, Diabetes mellitus (disorder), Mood, MAM, gamma-SG, Other ill-defined heart disease NOS (disorder), SCG3, Unspecified circulatory system disorder, Risk Factor, Quetelet Index, Other diseases of endocardium (disorder), Populations at Risk, [X]Other specified diseases of pericardium, Genetic, Having too much body fat, Other heart disease, Risk Score, obese-like, Other forms of heart disease, Overweight and obesity, Expressions, Other specified pericardial disease NOS, Population at Risk, BMI, cardiovascular disease, Loci, Social Risk Factor, Disease of cardiovascular system, Expression, constitutitional genetic, Diabetes, Circulatory system disease NOS, Methylations, diabetes, OTHER SEQUELAE OF MI NEC, Disease, Other ill-defined heart diseases, 35 kDa dystrophin-associated glycoprotein, Affects, not elsewhere classified, changes in DNA methylation, Factor, Disease affecting entire cardiovascular system (disorder), Risk Factor Scores, Cistrons, Other ill-defined heart disease, obesity, SGCG, LGMD2C, diabetes mellitus (disease), development, Cardiac Events, methylation, Other forms of heart disease (disorder), Other ill-defined heart disease NOS, PERICARDIAL DISEASE NEC, obesity disorder, Obesity (disorder), Relative Risk, Other specified diseases of pericardium, LEPROT, Cardiovascular, DMDA1, diabetes mellitus, Epigenomes, [X]Other ill-defined heart diseases, prophylaxis, Obesity NOS, Risks, postnatal growth, [X]Other forms of heart disease, Other sequelae of myocardial infarction, Locus, Risk Scores, Cardiovascular Disease, CVS disease, Other specified pericardial disease NOS (disorder), Quetelets Index, control, SCARMD2, Major Adverse Cardiac Events, hereditary, growth"],"pubmed_title_synonyms":["Quetelet Index, study, wide/broad, Epigenomes, Index, Methylomes, Obesity NOS, obesity disease, Adiposity, OBESITY NOS, Overweight and obesity, broad, DNA Methylomes, Adiposis, BMI, Obesity, Obese, wide, Quetelets Index, unspecified, obesity., Body Mass, Quetelet, Associations, Quetelet's Index, Obesity [Ambiguous], Obese (finding), DNA, Methylome, obesity disorder, Obesity (disorder), DNA Methylome"],"pubmed_abstract_synonyms":["Adult-Onset Diabetes Mellitus, type 2, Other diseases of pericardium (disorder), Materials, Cardiovascular disease, Product, Other pericardial disease NOS (disorder), FON1, Cardiovascular disorder, Suggestion, PAPILLARY MUSCLE DIS NEC, l(2)Sos, Type 2 Diabetes Mellitus, Etiology, growth and development, DNA Methylations, Biochemical Pathway, FLORAL ORGAN NUMBER 1, Relative, Prevention Intent, unspecified, Disease of cardiovascular system (disorder), Body Mass, Biological, Associations, Other heart disease NOS, Non-Insulin Dependent Diabetes Mellitus, Related, Biological Product, Cardiovascular Diseases, Adiposis., Project ENABLE, Widespread, Biologic Drugs, Involvement, Molecular, E(var)189, [X]Other forms of heart disease (disorder), Bdr, Tissue, Other ill-defined heart disease (disorder), Weights, Pathways, circulatory system disease, DNA Methylomes, SNAP-25, Ketosis-Resistant Diabetes Mellitus, NIDDM, metabolic, Noninsulin-Dependent, Diabetes mellitus, Disorder of cardiovascular system, Biological Medicine, Medicine, Relationship, Biologic Drug, INCREASED, Circulatory system disease NOS (disorder), Pathway, Index, Biologic Products, Methylomes, Adult-onset diabetes mellitus, familial, DmelCG7793, disease of subdivision of hemolymphoid system, Poorly marginated, DmIKKgamma, Adult-Onset Diabetes, dIKK, Relative Risks, Quetelet's Index, About, Obesity [Ambiguous], OBESITY, Cellular, numerical data, GENA70, dme-SOS, Educate, Ketosis Resistant, Maturity-Onset Diabetes Mellitus, CARDIOVASC DIS, Definite Attribution, Biological Medicines, Biological Drug, IKK-gamma, Type II Diabetes, Disorder of the circulatory system, Adiposity, [X]Other ill-defined heart diseases (disorder), OBESITY NOS, Biologics, Genomic, Condition, Phenotypes, non-insulin-dependent, People, Material, ILL-DEFINED HRT DIS NEC, etiology, Nepal Bhasa, DNA, Disease affecting entire cardiovascular system, Slow-Onset, DNA Methylome, FLORAL DEFECTIVE 10, T2DM - Type 2 Diabetes mellitus, lipids, Clinical Batch, Cardiovascular system disease, Genetic Locus, Biologic Pharmaceuticals, obesity disease, SUPERMAN, Other diseases of pericardium, EK2-8, Other disorders of papillary muscle, Adverse, Maturity-onset diabetes, dIKK-gamma, unspecified (disorder), Affected, Disorder of cardiovascular system (disorder), Cardiac, New Lesion, DmIKK-gamma, Projections and Predictions, Other ill-defined heart disease NOS (disorder), Unspecified circulatory system disorder, Biologicals, Pervasive, Clinical, Supply, Other forms of heart 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circulatory system, lipoprotein metabolism, Metabolic Network, results, Noninsulin-dependent diabetes mellitus, Adult-Onset, Consequence, Involved, single-organism transport, Biopharmaceuticals, Lipid, Obese (finding), Adverse Cardiac Event, Kenny, Genetic Materials, Biologic Product, NOS, Other pericardial disease NOS, Adverse Event Definitely Related to Intervention, Adverse Event Related to Intervention, regulator, Methylome, Genetic Material, br24, CIRCULATORY DISEASE NOS, dSos, br25, Clinical Data, Risk, 34Ea, Metabolized, Adverse Cardiac Events, Type 2, Features, SDTM Version 1.5, Noninsulin-Dependent Diabetes Mellitus, type II, wide, DmelCG16910, Non-Insulin Dependent Diabetes, Cistron, Measures and Weights, inherited genetic, DIFFUSE, molecular pathway, Methylation, Provided, Cardiovascular Disorders, ASCVD, Noninsulin Dependent, Other heart disease (disorder), Gene, broad, DIABETES MELLITUS TYPE 02, Obesity, [X]Cardiovascular disease, Relations, utilization, Metabolism, 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development, Cardiac Events, Characteristic, Clinical Lot, ENABLE, l(2)k05224, Type 2 Diabetes Mellitus Non-Insulin Dependent, methylation, Other forms of heart disease (disorder), PERICARDIAL DISEASE NEC, obesity disorder, Type 2 Diabetes, Metabolic, Epigenomes, Scales, Risks, EY2-3, FLO10, HERP, Cardiovascular Disease, Drug, Su(tor)2-2, Other specified pericardial disease NOS (disorder), Increase, SNAP, Natural Products, Major Adverse Cardiac Events, Type II, Future, growth, Maturity Onset, Genome, Advise Before Life Ends, Positive Margins"],"additional_accession":[]},"is_claimable":false,"name":"DNA methylation and the adverse metabolic outcomes of adiposity","description":"Overweight and obesity affect ~1.5 billion people worldwide, and are major risk factors for type-2 diabetes (T2D), cardiovascular disease and related metabolic and inflammatory disturbances.1,2 Although the mechanisms linking adiposity to its clinical sequelae are poorly understood, recent studies suggest that adiposity may influence DNA methylation,3-6 a key regulator of gene expression and molecular phenotype.7 Here we use epigenome-wide association to show that body mass index (BMI, a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci at P<1x10-7, range P=9.2x10-8 to 6.0x10-46; N=10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find the methylation loci are enriched for functional genomic features in multiple tissues (P<0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P<9.0x10-6, range P=5.5x10-6 to 6.1x10-35, N=1,785 samples). The methylation loci identified highlight genes involved in lipid and lipoprotein metabolism, substrate transport, and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future type-2 diabetes (relative risk per 1SD increase in Methylation Risk Score: 2.3 [2.07-2.56]; P=1.1x10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type-2 diabetes and other adverse clinical consequences of obesity.","dates":{"updated":"2017-07-26 15:39:29"},"accession":"EGAS00001001922","cross_references":{"TAXONOMY":["9606"],"pubmed":["28002404"],"EGA":["EGAD00010001029","EGAC00001000514"]}}