New genetic loci link adipose and insulin biology to body fat distribution.
187 - 196
MetadataShow full item record
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 × 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.
AuthorsShungin, D; Winkler, TW; Croteau-Chonka, DC; Ferreira, T; Locke, AE; Mägi, R; Strawbridge, RJ; Pers, TH; Fischer, K; Justice, AE; Workalemahu, T; Wu, JMW; Buchkovich, ML; Heard-Costa, NL; Roman, TS; Drong, AW; Song, C; Gustafsson, S; Day, FR; Esko, T; Fall, T; Kutalik, Z; Luan, J; Randall, JC; Scherag, A; Vedantam, S; Wood, AR; Chen, J; Fehrmann, R; Karjalainen, J; Kahali, B; Liu, C-T; Schmidt, EM; Absher, D; Amin, N; Anderson, D; Beekman, M; Bragg-Gresham, JL; Buyske, S; Demirkan, A; Ehret, GB; Feitosa, MF; Goel, A; Jackson, AU; Johnson, T; Kleber, ME; Kristiansson, K; Mangino, M; Mateo Leach, I; Medina-Gomez, C; Palmer, CD; Pasko, D; Pechlivanis, S; Peters, MJ; Prokopenko, I; Stančáková, A; Ju Sung, Y; Tanaka, T; Teumer, A; Van Vliet-Ostaptchouk, JV; Yengo, L; Zhang, W; Albrecht, E; Ärnlöv, J; Arscott, GM; Bandinelli, S; Barrett, A; Bellis, C; Bennett, AJ; Berne, C; Blüher, M; Böhringer, S; Bonnet, F; Böttcher, Y; Bruinenberg, M; Carba, DB; Caspersen, IH; Clarke, R; Daw, EW; Deelen, J; Deelman, E; Delgado, G; Doney, ASF; Eklund, N; Erdos, MR; Estrada, K; Eury, E; Friedrich, N; Garcia, ME; Giedraitis, V; Gigante, B; Go, AS; Golay, A; Grallert, H; Grammer, TB; Gräßler, J; Grewal, J; Groves, CJ; Haller, T; Hallmans, G; et al.
- College Publications 
Showing items related by title, author, creator and subject.
Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study. Prins, BP; Abbasi, A; Wong, A; Vaez, A; Nolte, I; Franceschini, N; Stuart, PE; Guterriez Achury, J; Mistry, V; Bradfield, JP;... (2016-06-21)BACKGROUND: C-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal. METHODS AND FINDINGS: We performed Mendelian ...
Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Surendran, P; Drenos, F; Young, R; Warren, H; Cook, JP; Manning, AK; Grarup, N; Sim, X; Barnes, DR; Witkowska, K;... (2016-07-26)High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we ...
Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Warren, HR; Evangelou, E; Cabrera, CP; Gao, H; Ren, M; Mifsud, B; Ntalla, I; Surendran, P; Liu, C; Cook, JP;... (2017-01-30)Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of ...