A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
| Title: | A genome-wide association study reveals variants in ARL15 that influence adiponectin levels. |
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| Authors: | J Brent Richards, Dawn Waterworth, Stephen O'Rahilly, Marie-France Hivert, Ruth J F Loos, John R B Perry, Toshiko Tanaka, Nicholas John Timpson, Robert K Semple, Nicole Soranzo, Kijoung Song, Nuno Rocha, Elin Grundberg, Josée Dupuis, Jose C Florez, Claudia Langenberg, Inga Prokopenko, Richa Saxena, Robert Sladek, Yurii Aulchenko, David Evans, Gerard Waeber, Jeanette Erdmann, Mary-Susan Burnett, Naveed Sattar, Joseph Devaney, Christina Willenborg, Aroon Hingorani, Jaquelin C M Witteman, Peter Vollenweider, Beate Glaser, Christian Hengstenberg, Luigi Ferrucci, David Melzer, Klaus Stark, John Deanfield, Janina Winogradow, Martina Grassl, Alistair S Hall, Josephine M Egan, John R Thompson, Sally L Ricketts, Inke R König, Wibke Reinhard, Scott Grundy, H-Erich Wichmann, Phil Barter, Robert Mahley, Y Antero Kesaniemi, Daniel J Rader, Muredach P Reilly, Stephen E Epstein, Alexandre F R Stewart, Cornelia M Van Duijn, Heribert Schunkert, Keith Burling, Panos Deloukas, Tomi Pastinen, Nilesh J Samani, Ruth McPherson, George Davey Smith, Timothy M Frayling, Nicholas J Wareham, James B Meigs, Vincent Mooser, Tim D Spector, GIANT Consortium |
| Source: | PLoS Genetics, Vol 5, Iss 12, p e1000768 (2009) |
| Publisher Information: | Public Library of Science (PLoS), 2009. |
| Publication Year: | 2009 |
| Collection: | LCC:Genetics |
| Subject Terms: | Genetics, QH426-470 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7390 1553-7404 |
| Relation: | http://europepmc.org/articles/PMC2781107?pdf=render; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404 |
| DOI: | 10.1371/journal.pgen.1000768 |
| Access URL: | https://doaj.org/article/5ebadbaada2a4a9caf70475a98073cf4 |
| Accession Number: | edsdoj.5ebadbaada2a4a9caf70475a98073cf4 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15537390 15537404 |
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| DOI: | 10.1371/journal.pgen.1000768 |
| Published in: | PLoS Genetics |
| Language: | English |