New genetic loci link adipose and insulin biology to body fat distribution
Publication date
2015-02-12
Authors
Shungin, Dmitry
Winkler, Thomas W.
Croteau-Chonka, Damien C.
Ferreira, Teresa
Lockes, Adam E.
Maegi, Reedik
Strawbridge, Rona J.
Pers, Tune H.
Fischer, Krista
Justice, Anne E.
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Supervisors
Document Type
Article
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taverne
Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P <5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Keywords
GENOME-WIDE ASSOCIATION, MESENCHYMAL STEM-CELLS, HUMAN HEIGHT, ADIPOGENIC DIFFERENTIATION, ABDOMINAL ADIPOSITY, SUSCEPTIBILITY LOCI, SEXUAL-DIMORPHISM, GLYCEMIC TRAITS, FALSE DISCOVERY, COMMON SNPS, Taverne
Citation
Shungin, D, Winkler, T W, Croteau-Chonka, D C, Ferreira, T, Lockes, A E, Maegi, R, Strawbridge, R J, Pers, T H, Fischer, K, Justice, A E, Workalemahu, T, Wu, J M W, Buchkovich, M L, Heard-Costa, N L, Roman, T S, Drong, A W, Song, C, Gustafsson, S, Day, F R, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J C, Scherag, A, Vedantam, S, Wood, A R, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C-T, Schmidt, E M, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg-Gresham, J L, Buyske, S, Demirkan, A, Ehret, G B, Feitosa, M F, Goel, A, Jackson, A U, Johnson, T, Kleber, M E, ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, GLGC, ICBP, Int Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium & ReproGen Consortium 2015, 'New genetic loci link adipose and insulin biology to body fat distribution', Nature, vol. 518, no. 7538, pp. 187-196. https://doi.org/10.1038/nature14132