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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.
Authors: Richards, JB
Waterworth, D
O'Rahilly, S
Hivert, MF
Loos, RJ
Perry, JR
Tanaka, T
Timpson, NJ
Semple, RK
Soranzo, N
Song, K
Rocha, N
Grundberg, E
Dupuis, J
Florez, JC
Langenberg, C
Prokopenko, I
Saxena, R
Sladek, R
Aulchenko, Y
Evans, D
Waeber, G
Erdmann, J
Burnett, MS
Sattar, N
Devaney, J
Willenborg, C
Hingorani, A
Witteman, JC
Vollenweider, P
Glaser, B
Hengstenberg, C
Ferrucci, L
Melzer, D
Stark, K
Deanfield, J
Winogradow, J
Grassl, M
Hall, AS
Egan, JM
Thompson, JR
Ricketts, SL
König, IR
Reinhard, W
Grundy, S
Wichmann, HE
Barter, P
Mahley, R
Kesaniemi, YA
Rader, DJ
Reilly, MP
Epstein, SE
Stewart, AF
Van Duijn, CM
Schunkert, H
Burling, K
Deloukas, P
Pastinen, T
Samani, NJ
McPherson, R
Davey Smith, G
Frayling, TM
Wareham, NJ
Meigs, JB
Mooser, V
Spector, TD
GIANT Consortium
Item Type: Journal Article
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< 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.
Issue Date: 1-Dec-2009
URI: http://hdl.handle.net/10044/1/28586
DOI: https://dx.doi.org/10.1371/journal.pgen.1000768
Start Page: e1000768
Journal / Book Title: PLoS Genet
Volume: 5
Issue: 12
Copyright Statement: © 2009 Richards et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Adiponectin
Coronary Disease
Diabetes Mellitus, Type 2
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
GIANT Consortium
Developmental Biology
0604 Genetics
Publication Status: Published
Conference Place: United States
Appears in Collections:School of Public Health