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Richards, J.B.* ; Waterworth, D.* ; O'Rahilly, S.* ; Hivert, M.F.* ; Loos, R.J.F.* ; Perry, J.R.B.* ; Tanaka, T.* ; Timpson, N.J.* ; Semple, R.K.* ; Soranzo, N.* ; Song, K.* ; Rocha, N.* ; Grundberg, E.* ; Dupuis, J.* ; Florez, J.C* ; Langenberg, C.* ; Prokopenko, I.* ; Saxena, R.* ; Aulchenko, Y.* ; Evans, D.* ; Waeber, G.* ; Erdmann, J.* ; Burnett, M.S.* ; Sattar, N.* ; Devaney, J.* ; Willenborg, C.* ; Hingorani, A.* ; Witteman, J.C.M.* ; Vollenweider, P.* ; Glaser, B.* ; Hengstenberg, C.* ; Ferrucci, L.* ; Melzer, D.* ; Stark, K.* ; Deanfield, J.* ; Winogradow, J.* ; Grassl, M.* ; Hall, A.S.* ; Egan, J.M.* ; Thompson, J.R.* ; Ricketts, S.L.* ; König, I.R.* ; Reinhard, W.* ; Grundy, S.* ; Wichmann, H.-E. ; Barter, P.* ; Mahley, R.* ; Kesaniemi, Y.A.* ; Rader, D.J.* ; Reilly, M.P.* ; Epstein, S.E.* ; Stewart, A.F.R.* ; van Duijn, C.M.* ; Schunkert, H.* ; Burling, K.* ; Deloukas, P.* ; Pastinen, T.* ; Samani, N.J.* ; McPherson, R.* ; Smith, G.D.* ; Frayling, T.M.* ; Wareham, N.J.* ; Meigs, J.B.* ; Mooser, V.* ; Spector, T.D.*

A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.

PLoS Genet. 5:e1000768 (2009)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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< or =5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =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 = 9.2x10(-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 = 2.9x10(-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 = 8.5x10(-6), n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords MOLECULAR-WEIGHT ADIPONECTIN; BONE-MINERAL DENSITY; SMALL G-PROTEINS; INSULIN-RESISTANCE; PLASMA ADIPONECTIN; METABOLIC SYNDROME; CIRCULATING ADIPONECTIN; MYOCARDIAL-INFARCTION; SERUM CONCENTRATION; APM1 GENE
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 5, Issue: 12, Pages: , Article Number: e1000768 Supplement: ,
Publisher Public Library of Science (PLoS)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)