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

Pubmed ID: 25935004

Pubmed Central ID: PMC4492394

Journal: Human molecular genetics

Publication Date: Aug. 1, 2015

Affiliation: Human Genetics Center, School of Public Health, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

MeSH Terms: Humans, Male, Female, Aged, Middle Aged, Body Mass Index, Genome-Wide Association Study, Obesity, Waist Circumference, Atherosclerosis, DNA Methylation, Epigenesis, Genetic, Lipid Metabolism, Metabolic Networks and Pathways, White People, Black or African American

Grants: N01-HC-25195, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, 5RC2HL102419, U01 HL072524, U01HL072524-04, R01 HL104135

Authors: Pankow JS, Li Y, Guan W, Deloukas P, Demerath EW, Boerwinkle E, Fornage M, Grove ML, Arnett DK, Aslibekyan S, Mendelson M, Zhou YH, Hedman ÅK, Sandling JK, Li LA, Irvin MR, Zhi D, Liang L, Liu C, Bressler J, Spector TD, North K, Absher DM, Levy D

Cite As: Demerath EW, Guan W, Grove ML, Aslibekyan S, Mendelson M, Zhou YH, Hedman ÅK, Sandling JK, Li LA, 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. Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci. Hum Mol Genet 2015 Aug 1;24(15):4464-79. Epub 2015 May 1.

Studies:

Abstract

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.