Fiche publication
Date publication
avril 2019
Journal
Diabetes
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MEYRE David
Tous les auteurs :
Wang DX, Kaur Y, Alyass A, Meyre D
Lien Pubmed
Résumé
We hypothesized that monogenic syndromic obesity genes are also involved in the polygenic variation of BMI. Single-marker, tag single nucleotide polymorphism (tagSNP) and gene-based analysis were performed on common variants near 54 syndromic obesity genes. We used publicly available data from meta-analyses of European BMI genome-wide association studies conducted by the Genetic Investigation of ANthropometric Traits (GIANT) Consortium and the UK Biobank (UKB) ( = 681,275 adults). A total of 33 loci were identified, of which 19 of 33 (57.6%) were located at SNPs previously identified by the GIANT Consortium and UKB meta-analysis, 11 of 33 (33.3%) were located at novel SNPs, and 3 of 33 (9.1%) were novel genes identified with gene-based analysis. Both single-marker and tagSNP analyses mapped the previously identified 19 SNPs by the GIANT Consortium and UKB meta-analysis. Gene-based analysis confirmed 15 of 19 (78.9%) of the novel SNPs' associated genes. Of the 11 novel loci, 8 were identified with single-marker analysis and the remaining 3 were identified with tagSNP analysis. Gene-based analysis confirmed 4 of 11 (36.3%) of these loci. Meta-analysis with the Early Growth Genetics (EGG) Consortium ( = 35,668 children) was conducted post hoc for top SNPs, confirming 17 of 33 (51.5%) loci, of which 5 were novel. This study supports evidence for a continuum between rare monogenic syndromic and common polygenic forms of obesity.
Mots clés
Adult, Body Mass Index, Body Weight, genetics, Child, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Obesity, genetics, Phenotype, Polymorphism, Single Nucleotide, White People, genetics
Référence
Diabetes. 2019 04;68(4):724-732
