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 circulating leptin levels. The EFO term leptin 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: leptin measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

TO Kilpeläinen, JF Carli, AA Skowronski, Q Sun, J Kriebel, MF Feitosa, ÅK Hedman, AW Drong, JE Hayes, J Zhao, TH Pers, U Schick, N Grarup, Z Kutalik, S Trompet, M Mangino, K Kristiansson, M Beekman, LP Lyytikäinen, J Eriksson, P Henneman, J Lahti, T Tanaka, J Luan, F Del Greco M, D Pasko, F Renström, SM Willems, A Mahajan, LM Rose, X Guo, Y Liu, ME Kleber, L Pérusse, T Gaunt, TS Ahluwalia, Y Ju Sung, YF Ramos, N Amin, A Amuzu, I Barroso, C Bellis, J Blangero, BM Buckley, S Böhringer, YD I Chen, AJ de Craen, DR Crosslin, CE Dale, Z Dastani, FR Day, J Deelen, GE Delgado, A Demirkan, FM Finucane, I Ford, ME Garcia, C Gieger, S Gustafsson, G Hallmans, SE Hankinson, AS Havulinna, C Herder, D Hernandez, AA Hicks, DJ Hunter, T Illig, E Ingelsson, A Ioan-Facsinay, JO Jansson, NS Jenny, ME Jørgensen, T Jørgensen, M Karlsson, W Koenig, P Kraft, J Kwekkeboom, T Laatikainen, KH Ladwig, CA LeDuc, G Lowe, Y Lu, P Marques-Vidal, C Meisinger, C Menni, AP Morris, RH Myers, S Männistö, MA Nalls, L Paternoster, A Peters, AD Pradhan, T Rankinen, LJ Rasmussen-Torvik, W Rathmann, TK Rice, J Brent Richards, PM Ridker, N Sattar, DB Savage, S Söderberg, NJ Timpson, L Vandenput, D van Heemst, HW Uh, MC Vohl, M Walker, HE Wichmann, E Widén, AR Wood, J Yao, T Zeller, Y Zhang, I Meulenbelt, M Kloppenburg, A Astrup, TI Sørensen, MA Sarzynski, DC Rao, P Jousilahti, E Vartiainen, A Hofman, F Rivadeneira, AG Uitterlinden, E Kajantie, C Osmond, A Palotie, JG Eriksson, M Heliövaara, PB Knekt, S Koskinen, A Jula, M Perola, RK Huupponen, JS Viikari, M Kähönen, T Lehtimäki, OT Raitakari, D Mellström, M Lorentzon, JP Casas, S Bandinelli, W März, A Isaacs, KW van Dijk, CM van Duijn, TB Harris, C Bouchard, MA Allison, DI Chasman, C Ohlsson, L Lind, RA Scott, C Langenberg, NJ Wareham, L Ferrucci, TM Frayling, PP Pramstaller, IB Borecki, DM Waterworth, S Bergmann, G Waeber, P Vollenweider, H Vestergaard, T Hansen, O Pedersen, FB Hu, P Eline Slagboom, H Grallert, TD Spector, JW Jukema, RJ Klein, EE Schadt, PW Franks, CM Lindgren, RL Leibel, RJ Loos

TITLE:

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

JOURNAL:

Nature communications Feb 2016, Vol 7, pp. 10494

ABSTRACT:

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PUBMED: 26833098
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