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 A Levy; James D. Stewart; Andrea Baccarelli; Lifang Hou; Karen N. Conneely; Trevor Anthony Mori; Lawrence Joseph Beilin; Rae‐Chi Huang; Penny Gordon‐Larsen; Annie Green Howard; Kari E. North

doi:10.2217/epi-2019-0276

GenomicsEpigenomicsSep 1, 2020

Peer-reviewed journal article

Methylome-Wide Association Study Of Central Adiposity Implicates Genes Involved In Immune And Endocrine Systems

Anne E. Justice iD, Geetha Chittoor iD, Rahul Gondalia iD, Phillip E. Melton iD, Elise Lim iD, Megan L. Grove iD, Eric A. Whitsel iD, Ching‐Ti Liu iD, L. Adrienne Cupples iD, Lindsay Fernández‐Rhodes iD, Weihua Guan iD, Jan Bressler iD, Myriam Fornage iD, Eric Boerwinkle iD, Yun Li iD, Ellen W. Demerath iD, Nancy L. Heard‐Costa iD, Daniel A Levy iD, James D. Stewart iD, Andrea Baccarelli iD, Lifang Hou iD, Karen N. Conneely iD, Trevor Anthony Mori iD, Lawrence Joseph Beilin iD, Rae‐Chi Huang iD, , Kari E. North iD

Abstract

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. We validated significantly associated Cytosine-phosphate-Guanine methylation sites (CpGs) among adults using the Womens Health Initiative and Framingham Heart Study participants (combined N=5743) and generalized associations in adolescents from The Raine Study (N=820). We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and 2 in adolescents, including CpG site associations near TXNIP, ADCY7, SREBF1, and RAP1GAP2 that had not previously been associated with obesity-related traits.

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