Methylome-Wide Association Study of Central Adiposity Implicates Genes Involved in Immune and Endocrine Systems
Anne E. Justice, Geetha Chittoor, Rahul Gondalia, Phillip E. Melton, Elise Lim, Megan L. Grove, Eric A. Whitsel, Ching‐Ti Liu, L. Adrienne Cupples, Lindsay Fernández‐Rhodes, Weihua Guan, Jan Bressler, Myriam Fornage, Eric Boerwinkle, Yun Li, Ellen W. Demerath, Nancy L. Heard‐Costa, Daniel Levy, James D. Stewart, Andrea Baccarelli, Lifang Hou, Karen N. Conneely, Trevor A. Mori, Lawrence J. Beilin, Rae‐Chi Huang, Penny Gordon‐Larsen, Annie Green Howard, Kari E. North
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.