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Title: A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels
Authors: 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.
subject: cardiovascular disorders;Congenital heart disease;diabetes and endocrinology;Obesity;type 2 diabetes;Genetics and Genomics;genetics of disease
Year: 2009
Publisher: Public Library of Science
Description: 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.
Standard no: 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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