Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism.
Adult
Animals
Bayes Theorem
Cohort Studies
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ metabolism
Female
Genome-Wide Association Study
Homeodomain Proteins
/ genetics
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
Risk Factors
Transcription Factors
/ genetics
Triglycerides
/ metabolism
Weight Loss
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
15
04
2017
accepted:
07
01
2019
entrez:
3
2
2019
pubmed:
3
2
2019
medline:
2
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30710084
doi: 10.1038/s41467-019-08492-8
pii: 10.1038/s41467-019-08492-8
pmc: PMC6358625
doi:
Substances chimiques
Drosophila Proteins
0
HGTX protein, Drosophila
0
Homeodomain Proteins
0
Nkx6-3 protein, human
0
Transcription Factors
0
Triglycerides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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