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Speliotes EK Willer CJ Berndt SI Monda KL Thorleifsson G Jackson AU Lango Allen H Lindgren CM Luan J Mägi R Randall JC Vedantam S Winkler TW Qi L Workalemahu T Heid IM Steinthorsdottir V Stringham HM Weedon MN Wheeler E Wood AR Ferreira T Weyant RJ Segrè AV Estrada K Liang L Nemesh J Park JH Gustafsson S Kilpeläinen TO Yang J Bouatia-Naji N Esko T Feitosa MF Kutalik Z Mangino M Raychaudhuri S Scherag A Smith AV Welch R Zhao JH Aben KK Absher DM Amin N Dixon AL Fisher E Glazer NL Goddard ME 《Nature genetics》2010,42(11):937-948
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10??), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. 相似文献
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Heid IM Jackson AU Randall JC Winkler TW Qi L Steinthorsdottir V Thorleifsson G Zillikens MC Speliotes EK Mägi R Workalemahu T White CC Bouatia-Naji N Harris TB Berndt SI Ingelsson E Willer CJ Weedon MN Luan J Vedantam S Esko T Kilpeläinen TO Kutalik Z Li S Monda KL Dixon AL Holmes CC Kaplan LM Liang L Min JL Moffatt MF Molony C Nicholson G Schadt EE Zondervan KT Feitosa MF Ferreira T Lango Allen H Weyant RJ Wheeler E Wood AR;MAGIC Estrada K Goddard ME Lettre G Mangino M Nyholt DR Purcell S 《Nature genetics》2010,42(11):949-960
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10?? to P = 1.8 × 10???) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10?3 to P = 1.2 × 10?13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. 相似文献
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile 总被引:1,自引:0,他引:1
Kilpeläinen TO Zillikens MC Stančákova A Finucane FM Ried JS Langenberg C Zhang W Beckmann JS Luan J Vandenput L Styrkarsdottir U Zhou Y Smith AV Zhao JH Amin N Vedantam S Shin SY Haritunians T Fu M Feitosa MF Kumari M Halldorsson BV Tikkanen E Mangino M Hayward C Song C Arnold AM Aulchenko YS Oostra BA Campbell H Cupples LA Davis KE Döring A Eiriksdottir G Estrada K Fernández-Real JM Garcia M Gieger C Glazer NL Guiducci C Hofman A Humphries SE Isomaa B Jacobs LC Jula A Karasik D Karlsson MK 《Nature genetics》2011,43(8):753-760
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. 相似文献
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