1. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels
- Author
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Richards, J.B. (Brent), Waterworth, D. (Dawn), O'Rahilly, S. (Stephen), Hivert, M.-F. (Marie-France), Loos, R.J.F. (Ruth), Perry, J.R.B. (John), Tanaka, T. (Toshiko), Timpson, N.J. (Nicholas), Semple, R.K. (Robert), Soranzo, N. (Nicole), Song, K. (Kijoung), Rocha, N. (Nuno), Grundberg, E. (Elin), Dupuis, J. (Josée), Florez, J.C. (Jose), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Sladek, R. (Rob), Aulchenko, Y.S. (Yurii), Evans, D.M. (David), Waeber, G. (Gérard), Burnett, M.S., Sattar, N. (Naveed), Devaney, J. (Joseph), Willenborg, C. (Christina), Hingorani, A. (Aroon), Witteman, J.C.M. (Jacqueline), Vollenweider, P. (Peter), Glaser, B. (Beate), Hengstenberg, C. (Christian), Ferrucci, L. (Luigi), Melzer, D. (David), Stark, K. (Klaus), Deanfield, J. (John), Winogradow, J. (Janina), Grassl, M. (Martina), Hall, A.S. (Alistair), Egan, J.M. (Josephine), Thompson, J.R. (John), Ricketts, S.L. (Sally), König, I.R. (Inke), Reinhard, W. (Wibke), Grundy, S.M. (Scott), Wichmann, H.E. (Heinz Erich), Barter, P. (Phil), Mahley, R. (Robert), Kesaniemi, Y.A. (Antero), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), Epstein, S.E. (Stephen), Stewart, A.F.R. (Alexandre), Tikka-Kleemola, P. (Päivi), Schunkert, H. (Heribert), Burling, K.A. (Keith), Erdmann, J. (Jeanette), Deloukas, P. (Panagiotis), Pastinen, T. (Tomi), Samani, N.J. (Nilesh), McPherson, R. (Ruth), Smith, A.V. (Davey), Frayling, T.M. (Timothy), Wareham, N.J. (Nick), Meigs, J.B. (James), Mooser, V. (Vincent), Spector, T.D. (Timothy), Richards, J.B. (Brent), Waterworth, D. (Dawn), O'Rahilly, S. (Stephen), Hivert, M.-F. (Marie-France), Loos, R.J.F. (Ruth), Perry, J.R.B. (John), Tanaka, T. (Toshiko), Timpson, N.J. (Nicholas), Semple, R.K. (Robert), Soranzo, N. (Nicole), Song, K. (Kijoung), Rocha, N. (Nuno), Grundberg, E. (Elin), Dupuis, J. (Josée), Florez, J.C. (Jose), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Sladek, R. (Rob), Aulchenko, Y.S. (Yurii), Evans, D.M. (David), Waeber, G. (Gérard), Burnett, M.S., Sattar, N. (Naveed), Devaney, J. (Joseph), Willenborg, C. (Christina), Hingorani, A. (Aroon), Witteman, J.C.M. (Jacqueline), Vollenweider, P. (Peter), Glaser, B. (Beate), Hengstenberg, C. (Christian), Ferrucci, L. (Luigi), Melzer, D. (David), Stark, K. (Klaus), Deanfield, J. (John), Winogradow, J. (Janina), Grassl, M. (Martina), Hall, A.S. (Alistair), Egan, J.M. (Josephine), Thompson, J.R. (John), Ricketts, S.L. (Sally), König, I.R. (Inke), Reinhard, W. (Wibke), Grundy, S.M. (Scott), Wichmann, H.E. (Heinz Erich), Barter, P. (Phil), Mahley, R. (Robert), Kesaniemi, Y.A. (Antero), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), Epstein, S.E. (Stephen), Stewart, A.F.R. (Alexandre), Tikka-Kleemola, P. (Päivi), Schunkert, H. (Heribert), Burling, K.A. (Keith), Erdmann, J. (Jeanette), Deloukas, P. (Panagiotis), Pastinen, T. (Tomi), Samani, N.J. (Nilesh), McPherson, R. (Ruth), Smith, A.V. (Davey), Frayling, T.M. (Timothy), Wareham, N.J. (Nick), Meigs, J.B. (James), Mooser, V. (Vincent), and Spector, T.D. (Timothy)
- 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 = 9.2×10-19for 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
- Published
- 2009
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