Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci.

TitleEpigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci.
Publication TypeJournal Article
Year of Publication2015
AuthorsDemerath, EW, Guan, W, Grove, ML, Aslibekyan, S, Mendelson, M, Zhou, Y-H, Hedman, ÅK, Sandling, JK, Li, L-A, Irvin, MR, Zhi, D, Deloukas, P, Liang, L, Liu, C, Bressler, J, Spector, TD, North, K, Li, Y, Absher, DM, Levy, D, Arnett, DK, Fornage, M, Pankow, JS, Boerwinkle, E
JournalHum Mol Genet
Date Published2015 Aug 01
KeywordsAged, Atherosclerosis, Black or African American, Body Mass Index, DNA Methylation, Epigenesis, Genetic, Female, Genome-Wide Association Study, Humans, Lipid Metabolism, Male, Metabolic Networks and Pathways, Middle Aged, Obesity, Waist Circumference, White People

Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 × 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.

Alternate JournalHum Mol Genet
PubMed ID25935004
PubMed Central IDPMC4492394
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
R01 HL104135 / HL / NHLBI NIH HHS / United States
5RC2HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
/ / Department of Health / United Kingdom
HHSN268201100010C / / PHS HHS / United States
U01 HL072524 / HL / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
U01HL072524-04 / HL / NHLBI NIH HHS / United States
/ / Wellcome Trust / United Kingdom

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