@article{1efaec5b5777415c8f4a7de650830749,
title = "Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism",
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 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.",
keywords = "LIFE-STYLE INTERVENTION, RISK-FACTORS, ASSOCIATION, MICRORNAS, REGAIN, LONG, TRANSCRIPTION, INSIGHTS, DISEASE, OBESITY",
author = "Armand Valsesia and Qiao-Ping Wang and Nele Gheldof and Jerome Carayol and Helene Ruffieux and Teleri Clark and Victoria Shenton and Oyston, \{Lisa J.\} and Gregory Lefebvre and Sylviane Metairon and Christian Chabert and Ondine Walter and Polina Mironova and Paulina Lau and Patrick Descombes and Nathalie Viguerie and Dominique Langin and Mary-Ellen Harper and Arne Astrup and Saris, \{Wim H.\} and Robert Dent and Neely, \{Greg G.\} and Joerg Hager",
note = "Funding Information: Competing interests: A.V., J.C., N.G., H.R., G.L., S.M., C.C., O.W., P.M., P.D. and J.H. are full-time employees at Nestl{\'e} Institute of Health Sciences SA. D.L. is a member of Institut Universitaire de France. W.H.S. reports having received research support from several food companies such as Nestle, DSM, Unilever, Nutrition et Sante and Danone as well as Pharmaceutical companies such as GSK, Novartis and Novo Nordisk. He is an unpaid scientific advisor for the International Life Science Institute, ILSI Europe. A.A. reports grants or personal fees from McCain Foods, USA, personal fees from McDonald{\textquoteright}s, USA, personal fees from Basic Research, USA, personal fees from Nestl{\'e}, Lausanne, personal fees from Dutch Beer Knowledge Institute, NL, personal fees from Gelesis, USA, personal fees from Novo Nordisk, DK, personal fees from S-Biotek, DK, grants from Arla Foods, DK, grants from Danish Dairy Research Council, grants from Nordea Foundation, DK, outside the submitted work; and Royalties received for the book first published in Danish as Verdens Bedste Kur (Politiken, Copenhagen) and subsequently published in Dutch as Het beste dieet ter wereld (Kosmos Uitgevers, Utrecht/Antwerpen), and in English as World{\textquoteright}s Best Diet (Penguin, Australia). G.N. is supported by an NHMRC career development fellowship II CDF1111940. The remaining authors declare no competing interests. Funding Information: We are grateful to Virginie Alexandre for useful scientific discussions and help with project management. We are also grateful to Olivier Simon, Radovan Chytracek, Richard Cote, and Kitsa Paluku for development of a clinical and omics data integration system. We thank Dr. Jan Veenstra for generous gifts of antibodies. The DiOGenes project was supported by the European Commission (Food Quality and Safety Priority of the Sixth Framework Program: FP6-2005-513946). Local sponsors made financial contributions to the shop centers, which also received a number of foods free of charge from food manufacturers. A full list of these sponsors can be seen at www.DiOGenes-eu.org/sponsors/. Functional analyses in fly were supported by the Australian government NHMRC (National Health and Medical Research Council) project grants APP1028887 and APP1124723. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = feb,
day = "1",
doi = "10.1038/s41467-019-08492-8",
language = "English",
volume = "10",
pages = "1--10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
number = "1",
}