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 Adiposity. The EFO term obesity 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: obesity

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

TO Kilpeläinen, MC Zillikens, A Stančákova, FM Finucane, JS Ried, C Langenberg, W Zhang, JS Beckmann, J Luan, L Vandenput, U Styrkarsdottir, Y Zhou, AV Smith, JH Zhao, N Amin, S Vedantam, SY Shin, T Haritunians, M Fu, MF Feitosa, M Kumari, BV Halldorsson, E Tikkanen, M Mangino, C Hayward, C Song, AM Arnold, YS Aulchenko, BA Oostra, H Campbell, LA Cupples, KE Davis, A Döring, G Eiriksdottir, K Estrada, JM Fernández-Real, M Garcia, C Gieger, NL Glazer, C Guiducci, A Hofman, SE Humphries, B Isomaa, LC Jacobs, A Jula, D Karasik, MK Karlsson, KT Khaw, LJ Kim, M Kivimäki, N Klopp, B Kühnel, J Kuusisto, Y Liu, O Ljunggren, M Lorentzon, RN Luben, B McKnight, D Mellström, BD Mitchell, V Mooser, JM Moreno, S Männistö, JR O'Connell, L Pascoe, L Peltonen, B Peral, M Perola, BM Psaty, V Salomaa, DB Savage, RK Semple, T Skaric-Juric, G Sigurdsson, KS Song, TD Spector, AC Syvänen, PJ Talmud, G Thorleifsson, U Thorsteinsdottir, AG Uitterlinden, CM van Duijn, A Vidal-Puig, SH Wild, AF Wright, DJ Clegg, E Schadt, JF Wilson, I Rudan, S Ripatti, IB Borecki, AR Shuldiner, E Ingelsson, JO Jansson, RC Kaplan, V Gudnason, TB Harris, L Groop, DP Kiel, F Rivadeneira, M Walker, I Barroso, P Vollenweider, G Waeber, JC Chambers, JS Kooner, N Soranzo, JN Hirschhorn, K Stefansson, HE Wichmann, C Ohlsson, S O'Rahilly, NJ Wareham, EK Speliotes, CS Fox, M Laakso, RJ Loos

TITLE:

Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

JOURNAL:

Nature genetics Jun 2011, Vol 43, pp. 753-60

ABSTRACT:

Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance. PUBMED: 21706003
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