Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_018C0E67910C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.
Périodique
Plos Genetics
Auteur(s)
Rueedi R., Ledda M., Nicholls A.W., Salek R.M., Marques-Vidal P., Morya E., Sameshima K., Montoliu I., Da Silva L., Collino S., Martin F.P., Rezzi S., Steinbeck C., Waterworth D.M., Waeber G., Vollenweider P., Beckmann J.S., Le Coutre J., Mooser V., Bergmann S., Genick U.K., Kutalik Z.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
10
Numéro
2
Pages
e1004132
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish pdf: Research Article
Résumé
Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/10/2014 14:57
Dernière modification de la notice
08/05/2019 13:42
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