A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels

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A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels

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Title: A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels
Author: Waterworth, Dawn; O'Rahilly, Stephen; Hivert, Marie-France; Loos, Ruth J. F.; Tanaka, Toshiko; Timpson, Nicholas John; Semple, Robert K.; Soranzo, Nicole; Song, Kijoung; Rocha, Nuno; Grundberg, Elin; Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Sladek, Robert; Aulchenko, Yurii; Waeber, Gerard; Erdmann, Jeanette; Burnett, Mary-Susan; Sattar, Naveed; Devaney, Joseph; Willenborg, Christina; Hingorani, Aroon; Witteman, Jaquelin C. M.; Vollenweider, Peter; Glaser, Beate; Hengstenberg, Christian; Ferrucci, Luigi; Melzer, David; Stark, Klaus; Deanfield, John; Winogradow, Janina; Grassl, Martina; Hall, Alistair S.; Egan, Josephine M.; Ricketts, Sally L.; König, Inke R.; Reinhard, Wibke; Grundy, Scott; Wichmann, H-Erich; Barter, Phil; Mahley, Robert; Kesaniemi, Y. Antero; Rader, Daniel J.; Reilly, Muredach P.; Stewart, Alexandre F. R.; Van Duijn, Cornelia M.; Schunkert, Heribert; Burling, Keith; Deloukas, Panos; Pastinen, Tomi; Samani, Nilesh J.; McPherson, Ruth; Davey Smith, George; Frayling, Timothy M.; Wareham, Nicholas J.; Mooser, Vincent; Spector, Tim D.; Richards, J. Brent; Florez, Jose Carlos; Perry, John R.B.; Saxena, Richa; Evans, David; Meigs, James Benjamin; Thompson, John R.; Epstein, Stephen E.

Note: Order does not necessarily reflect citation order of authors.

Citation: Richards, J. Brent, Dawn Waterworth, Stephen O'Rahilly, Marie-France Hivert, Ruth J. F. Loos, John R. B. Perry, Toshiko Tanaka, et al. 2009. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels. PLoS Genetics 5(12): e1000768.
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Abstract: The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P≤5×10−8). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P≤0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2×10−19 for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9×10−8, n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5×10−6, n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2×10−3, n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.
Published Version: doi:10.1371/journal.pgen.1000768
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781107/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4874764

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