DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Adiponectin levels. The EFO term adiponectin measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: adiponectin measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

JB Richards, D Waterworth, S O'Rahilly, MF Hivert, RJ Loos, JR Perry, T Tanaka, NJ Timpson, RK Semple, N Soranzo, K Song, N Rocha, E Grundberg, J Dupuis, JC Florez, C Langenberg, I Prokopenko, R Saxena, R Sladek, Y Aulchenko, D Evans, G Waeber, J Erdmann, MS Burnett, N Sattar, J Devaney, C Willenborg, A Hingorani, JC Witteman, P Vollenweider, B Glaser, C Hengstenberg, L Ferrucci, D Melzer, K Stark, J Deanfield, J Winogradow, M Grassl, AS Hall, JM Egan, JR Thompson, SL Ricketts, IR König, W Reinhard, S Grundy, HE Wichmann, P Barter, R Mahley, YA Kesaniemi, DJ Rader, MP Reilly, SE Epstein, AF Stewart, CM Van Duijn, H Schunkert, K Burling, P Deloukas, T Pastinen, NJ Samani, R McPherson, G Davey Smith, TM Frayling, NJ Wareham, JB Meigs, V Mooser, TD Spector

TITLE:

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

JOURNAL:

PLoS genetics Dec 2009, Vol 5, pp. e1000768

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. PUBMED: 20011104
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