Methylome-wide association study of central adiposity implicates genes involved in immune and endocrine systems

• Type of Material: Article
• Authors: Anne E Justice, Geisinger; Geetha Chittoor, Geisinger; Rahul Gondalia, University of North Carolina; Philip E Melton, University of Western Australia; Elise Lim, Boston University; Megan L Grove, Univ Texas Hlth Sci Ctr Houston; Eric A Whitsel, University of North Carolina; Ching-Ti Liu, Boston University; Adrienne L Cupples, Boston University; Lindsay Fernandez-Rhodes, University of North Carolina; Weihua Guan, University of Minnesota, Minneapolis; Jan Bressler, The University of Texas Health Science Center at Houston, Houston; Myriam Fornage, The University of Texas Health Science Center at Houston, Houston; Eric Boerwinkle, The University of Texas Health Science Center at Houston, Houston; Yun Li, University of North Carolina; Ellen Demerath, University of Minnesota, Minneapolis; Nancy Heard-Costa, Framingham Heart Study, Framingham; Dan Levy, NHLBI Framingham Heart Study, Framingham; James D Stewart, University of North Carolina; Andrea Baccarelli, Columbia University; Lifang Hou, Northwestern University; Karen Conneely, Emory University; Trevor A Mori, University of Western Australia; Lawrence J Beilin, University of Western Australia; Rae-Chi Huang, University of Western Australia; Penny Gordon-Larsen, University of North Carolina Chapel Hill; Annie Green Howard, University of North Carolina; Kari E North, University of North Carolina
• Language: English
• Date: 2020-09-09
• Publisher: FUTURE MEDICINE LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Future Medicine Ltd
• Final Published Version (URL): http://dx.doi.org/10.2217/epi-2019-0276
• Title of Journal or Parent Work: EPIGENOMICS
• Volume: 12
• Issue: 17
• Start Page: 1483
• End Page: 1499
• Keywords: PERIPHERAL-BLOOD; central adiposity; TXNIP; Genetics & Heredity; waist-to-height ratio; OBESITY; Life Sciences & Biomedicine; WAIST CIRCUMFERENCE; cardiometabolic disease; GTPASE-ACTIVATING PROTEIN; methylome-wide association study; waist-to-hip ratio; DNA methylation; LOCI; Science & Technology; body fat distribution; BODY-MASS INDEX; waist circumference; EPIGENOME-WIDE; BLOOD-PRESSURE; ancestrally diverse; DNA METHYLATION; EXPRESSION DATA
• Research Categories: Health Sciences, Pharmacy; Health Sciences, Epidemiology

Abstract

Aim: We conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist-to-hip ratio and waist-to-height ratio adjusted for body mass index, in 2684 African-American adults in the Atherosclerosis Risk in Communities study. Materials & methods: We validated significantly associated cytosine-phosphate-guanine methylation sites (CpGs) among adults using the Women's Health Initiative and Framingham Heart Study participants (combined n = 5743) and generalized associations in adolescents from The Raine Study (n = 820). Results & conclusion: We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and two in adolescents, including CpG site associations near TXNIP, ADCY7, SREBF1 and RAP1GAP2 that had not previously been associated with obesity-related traits.