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; Gregory Lefebvre; Sylviane Metairon; Christian Chabert; Ondine Walter; Polina Mironova; Paulina Lau; Patrick Descombes; Nathalie Viguerie; Dominique Langin; Mary-Ellen Harper; Arne Astrup; Wim H Saris; Robert Dent; Greg G Neely; Jörg Hager

doi:10.1038/s41467-019-08492-8

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, Gregory Lefebvre, Sylviane Metairon, Christian Chabert, Ondine Walter, Polina Mironova, Paulina Lau, Patrick Descombes, Nathalie Viguerie, Dominique Langin, Mary-Ellen Harper, Arne Astrup, Wim H SarisRobert Dent, Greg G Neely, Jörg Hager

Obesity Research

7 Citations (Scopus)

39 Downloads (Pure)

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.

Original language	English
Article number	540
Journal	Nature Communications
Volume	10
Number of pages	10
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-08492-8
Publication status	Published - 1 Dec 2019

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Valsesia et al_Nature Communications_2019_Vol 10_e540Final published version, 2.49 MBLicence: CC BY

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Valsesia, A., Wang, Q-P., Gheldof, N., Carayol, J., Ruffieux, H., Clark, T., Shenton, V., Oyston, L. J., Lefebvre, G., Metairon, S., Chabert, C., Walter, O., Mironova, P., Lau, P., Descombes, P., Viguerie, N., Langin, D., Harper, M-E., Astrup, A., ... Hager, J. (2019). Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism. Nature Communications, 10, [540]. https://doi.org/10.1038/s41467-019-08492-8

Valsesia, A, Wang, Q-P, Gheldof, N, Carayol, J, Ruffieux, H, Clark, T, Shenton, V, Oyston, LJ, Lefebvre, G, Metairon, S, Chabert, C, Walter, O, Mironova, P, Lau, P, Descombes, P, Viguerie, N, Langin, D, Harper, M-E, Astrup, A, Saris, WH, Dent, R, Neely, GG & Hager, J 2019, 'Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism', Nature Communications, vol. 10, 540. https://doi.org/10.1038/s41467-019-08492-8

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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.",

author = "Armand Valsesia and Qiao-Ping Wang and Nele Gheldof and J{\'e}r{\^o}me Carayol and H{\'e}l{\`e}ne 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 J{\"o}rg Hager",

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AU - Valsesia, Armand

AU - Wang, Qiao-Ping

AU - Gheldof, Nele

AU - Carayol, Jérôme

AU - Ruffieux, Hélène

AU - Clark, Teleri

AU - Shenton, Victoria

AU - Oyston, Lisa J

AU - Lefebvre, Gregory

AU - Metairon, Sylviane

AU - Chabert, Christian

AU - Walter, Ondine

AU - Mironova, Polina

AU - Lau, Paulina

AU - Descombes, Patrick

AU - Viguerie, Nathalie

AU - Langin, Dominique

AU - Harper, Mary-Ellen

AU - Astrup, Arne

AU - Saris, Wim H

AU - Dent, Robert

AU - Neely, Greg G

AU - Hager, Jörg

N1 - CURIS 2019 NEXS 036

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-019-08492-8

M3 - Journal article

C2 - 30710084

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

M1 - 540

ER -

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

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