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 Baccarelli; Lifang Hou; Karen Conneely; Trevor A Mori; Lawrence J Beilin; Rae-Chi Huang; Penny Gordon-Larsen; Annie Green Howard; Kari E North

doi:10.2217/epi-2019-0276

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

Epigenomics. 2020 Sep;12(17):1483-1499. doi: 10.2217/epi-2019-0276. Epub 2020 Sep 9.

Authors

Anne E Justice^{1

2}, Geetha Chittoor¹, Rahul Gondalia², Phillip E Melton^{3

4

5}, Elise Lim⁶, Megan L Grove⁷, Eric A Whitsel^{2

8}, Ching-Ti Liu⁶, L Adrienne Cupples^{6

9}, Lindsay Fernandez-Rhodes^{2

10}, Weihua Guan¹¹, Jan Bressler⁷, Myriam Fornage^{12

13}, Eric Boerwinkle^{7

14}, Yun Li^{15

16}, Ellen Demerath¹⁷, Nancy Heard-Costa^{9

18}, Dan Levy^{19

20}, James D Stewart², Andrea Baccarelli²¹, Lifang Hou²², Karen Conneely²³, Trevor A Mori²⁴, Lawrence J Beilin²⁴, Rae-Chi Huang²⁵, Penny Gordon-Larsen^{26

27}, Annie Green Howard^{15

27}, Kari E North^{2

27}

Affiliations

¹ Department of Population Health Sciences, Geisinger, Danville, PA 17822, USA.
² Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ School of Biomedical Science, Faculty of Health & Medical Sciences, The University of Western Australia, Perth, WA 6000, Australia.
⁴ School of Pharmacy & Biomedical Sciences, Faculty of Health Sciences, Curtin University, MRF Building, Perth, WA 6000, Australia.
⁵ Menzies Institute for Medical Research, College of Health & Medicine, University of Tasmania, Hobart, TA, 7000 Australia.
⁶ Department of Biostatistics, Boston University, Boston, MA 02118, USA.
⁷ Human Genetics Center, Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
⁸ Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁹ Framingham Heart Study, Framingham, MA, 01701, USA.
¹⁰ Department of Biobehavioral Health, Pennsylvania State University, University Park, PA 16802, USA.
¹¹ Division of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA.
¹² Center for Human Genetics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
¹³ Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.
¹⁴ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁵ Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁶ Department of Genetics, University of North Carolina at Chapel Hill, NC 27599, USA.
¹⁷ Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
¹⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
¹⁹ Population sciences branch, NHLBI Framingham Heart Study, Framingham, MA 01702, USA.
²⁰ Department of Medicine, Boston University, Boston, MA 02118, USA.
²¹ Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences & Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA.
²² Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University Chicago, Evanston, IL, USA.
²³ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
²⁴ Medical School, University of Western Australia, Perth, Australia.
²⁵ Telethon Kids Institute, University of Western Australia, Perth, Australia.
²⁶ Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC 27599, USA.
²⁷ Carolina Population Center, University of North Carolina at Chapel Hill, NC 27516, USA.

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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adiposity / genetics*
Cohort Studies
CpG Islands
DNA Methylation*
Disease Susceptibility
Endocrine System / metabolism*
Epigenesis, Genetic*
Epigenomics* / methods
Genome-Wide Association Study
Humans
Immune System / metabolism*
Obesity / genetics
Obesity / metabolism

Abstract

Publication types

MeSH terms

Grants and funding