Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism

Valsesia, Armand; Wang, Qiao‐Ping; Gheldof, Nele; Carayol, Jérôme; Ruffieux, Hélène; Clark, Teleri; Shenton, Victoria; Oyston, Lisa J.; Lefebvre, Grégory; Métairon, Sylviane; Chabert, Christian; Walter, Ondine; Mironova, Polina; Lau, Paulina; Descombes, Patrick; Viguerie, Nathalie; Langin, Dominique; Harper, Mary‐Ellen; Astrup, Arne; Saris, Wim H. M.; Dent, Robert; Neely, G. Gregory; Hager, Jörg

doi:10.1038/s41467-019-08492-8

articleNature CommunicationsFeb 1, 2019GOLD OA

Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism

AVArmand Valsesia QWQiao‐Ping Wang NGNele Gheldof JCJérôme Carayol HRHélène Ruffieux

Nestlé (Switzerland) · The University of Sydney · +13 more institutions

PubMed

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Abstract

Hundreds of genetic variants have been associated with Body Mass Index (BMI) through genome-wide association studies (GWAS) using observational cohorts. However, the genetic contribution to efficient weight loss in response to dietary intervention remains unknown. We perform a GWAS in two large low-caloric diet intervention cohorts of obese participants. Two loci close to NKX6.3/MIR486 and RBSG4 are identified in the Canadian discovery cohort (n = 1166) and replicated in the DiOGenes cohort (n = 789). Modulation of HGTX (NKX6.3 ortholog) levels in Drosophila melanogaster leads to significantly altered triglyceride levels. Additional tissue-specific experiments demonstrate an action through the oenocytes, fly…

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Keywords

Genome-wide association study
Biology
Genetic association
Drosophila melanogaster
Body mass index
Lipid metabolism
Genetics
Bioinformatics

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