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

Justice, A. E.; Chittoor, G.; Gondalia, R.; Melton, P. E.; Lim, E.; Grove, M. L.; Whitsel, E. A.; Liu, C.-T.; Cupples, L. A.; Fernandez-Rhodes, L.; Guan, W.; Bressler, J.; Fornage, M.; Boerwinkle, E.; Li, Y.; Demerath, E.; Heard-Costa, N.; Levy, D.; Stewart, J. D.; Baccarelli, A.; Hou, L.; Conneely, K.; Mori, T.; Beilin, L. J.; Huang, R.-C.; Gordon-Larsen, P.; Howard, A. G.; North, K. E.

doi:10.1101/766832

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bioRxiv · 10.1101/766832

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

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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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Justice, A. E., Chittoor, G., Gondalia, R., Melton, P. E., Lim, E., Grove, M. L., Whitsel, E. A., Liu, C.-T., Cupples, L. A., Fernandez-Rhodes, L., Guan, W., Bressler, J., Fornage, M., Boerwinkle, E., Li, Y., Demerath, E., Heard-Costa, N., Levy, D., Stewart, J. D., Baccarelli, A., Hou, L., Conneely, K., Mori, T., Beilin, L. J., Huang, R.-C., Gordon-Larsen, P., Howard, A. G., North, K. E.. 2019-09-12. Methylome-Wide Association Study Of Central Adiposity Implicates Genes Involved In Immune And Endocrine Systems. https://doi.org/10.1101/766832

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