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

Valsesia, ArmandWang, Qiao-PingGheldof, NeleCarayol, JeromeRuffieux, HeleneClark, TeleriShenton, VictoriaOyston, Lisa J.Lefebvre, GregoryMetairon, SylvianeChabert, ChristianWalter, OndineMironova, PolinaLau, PaulinaDescombes, PatrickViguerie, NathalieLangin, DominiqueHarper, Mary-EllenAstrup, ArneSaris, Wim H.Dent, RobertNeely, Greg G.Hager, Joerg2019-06-182019-06-182019-06-182019-02-0110.1038/s41467-019-08492-8https://infoscience.epfl.ch/handle/20.500.14299/158085WOS:000457440700005Hundreds 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 hepatocyte-like cells that regulate lipid metabolism. Our results identify genetic variants associated with the efficacy of weight loss in obese subjects and identify a role for NKX6.3 in lipid metabolism, and thereby possibly weight control.Multidisciplinary SciencesScience & Technology - Other Topicslife-style interventionrisk-factorsassociationmicrornasregainlongtranscriptioninsightsdiseaseobesityGenome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolismtext::journal::journal article::research article