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

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Serval ID
serval:BIB_018C0E67910C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.
Journal
Plos Genetics
Author(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
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
10
Number
2
Pages
e1004132
Language
english
Notes
Publication types: Journal Article Publication Status: epublish pdf: Research Article
Abstract
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
Yes
Create date
10/10/2014 13:57
Last modification date
20/08/2019 12:23
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