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

Author:

Justice Anne E12ORCID,Chittoor Geetha1,Gondalia Rahul2,Melton Phillip E345,Lim Elise6,Grove Megan L7,Whitsel Eric A28,Liu Ching-Ti6,Cupples L Adrienne69,Fernandez-Rhodes Lindsay210,Guan Weihua11,Bressler Jan7,Fornage Myriam1213,Boerwinkle Eric714,Li Yun1516,Demerath Ellen17,Heard-Costa Nancy918,Levy Dan1920,Stewart James D2,Baccarelli Andrea21,Hou Lifang22,Conneely Karen23,Mori Trevor A24,Beilin Lawrence J24,Huang Rae-Chi25,Gordon-Larsen Penny2627,Howard Annie Green1527,North Kari E227

Affiliation:

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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