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

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

doi:10.1038/s41467-019-08492-8

Abstract

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

Genome-wide association studyBiologyGenetic associationDrosophila melanogasterBody mass indexLipid metabolismGeneticsBioinformaticsMedicineInternal medicineSingle-nucleotide polymorphismGeneEndocrinologyGenotype

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Publication Info

Year: 2019
Type: article
Volume: 10
Issue: 1
Pages: 540-540
Citations: 1070
Access: Closed

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APA Style

                            
                                
                                    Armand Valsesia, 
                                
                                    Qiao‐Ping Wang, 
                                
                                    Nele Gheldof
                                
                                et al.
                            
                            (2019). 
                            Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism. 
                            Nature Communications
                            , 10
                            (1)
                            , 540-540.
                            https://doi.org/10.1038/s41467-019-08492-8
                        

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DOI: 10.1038/s41467-019-08492-8