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 Fernandez-Rhodes, Weihua Guan, Jan Bressler, Myriam Fornage, Eric Boerwinkle, Yun Li, Ellen Demerath, Nancy Heard-Costa, Dan Levy, James D. Stewart, Andrea BaccarelliLifang Hou, Karen Conneely, Trevor A. Mori, Lawrence J. Beilin, Rae Chi Huang, Penny Gordon-Larsen, Annie Green Howard, Kari E. North

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1483-1499
Number of pages17
JournalEpigenomics
Volume12
Issue number17
DOIs
StatePublished - Sep 2020

Keywords

  • DNA methylation
  • TXNIP
  • ancestrally diverse
  • body fat distribution
  • cardiometabolic disease
  • central adiposity
  • methylome-wide association study
  • waist circumference
  • waist-to-height ratio
  • waist-to-hip ratio

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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