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Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes

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Item Type:Article
Title:Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
Creators Name:Jäger, S. and Wahl, S. and Kröger, J. and Sharma, S. and Hoffmann, P. and Floegel, A. and Pischon, T. and Prehn, C. and Adamski, J. and Müller-Nurasyid, M. and Waldenberger, M. and Strauch, K. and Peters, A. and Gieger, C. and Suhre, K. and Grallert, H. and Boeing, H. and Schulze, M.B. and Meidtner, K.
Abstract:Diabetes-associated metabolites may aid the identification of new risk variants for type 2 diabetes. Using targeted metabolomics within a subsample of the German EPIC-Potsdam study (n = 2500), we tested previously published SNPs for their association with diabetes-associated metabolites and conducted an additional exploratory analysis using data from the exome chip including replication within 2,692 individuals from the German KORA F4 study. We identified a total of 16 loci associated with diabetes-related metabolite traits, including one novel association between rs499974 (MOGAT2) and a diacyl-phosphatidylcholine ratio (PC aa C40:5/PC aa C38:5). Gene-based tests on all exome chip variants revealed associations between GFRAL and PC aa C42:1/PC aa C42:0, BIN1 and SM (OH) C22:2/SM C18:0 and TFRC and SM (OH) C22:2/SM C16:1). Selecting variants for gene-based tests based on functional annotation identified one additional association between OR51Q1 and hexoses. Among single genetic variants consistently associated with diabetes-related metabolites, two (rs174550 (FADS1), rs3204953 (REV3L)) were significantly associated with type 2 diabetes in large-scale meta-analysis for type 2 diabetes. In conclusion, we identified a novel metabolite locus in single variant analyses and four genes within gene-based tests and confirmed two previously known mGWAS loci which might be relevant for the risk of type 2 diabetes.
Keywords:Alleles, Biomarkers, Exome, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Heritable, Quantitative Trait, Metabolome, Metabolomics, Oligonucleotide Array Sequence Analysis, Quantitative Trait Loci, Single Nucleotide, Polymorphism, Type 2,Diabetes Mellitus
Source:Scientific Reports
ISSN:2045-2322
Publisher:Nature Publishing Group
Volume:7
Number:1
Page Range:6037
Date:20 July 2017
Official Publication:https://doi.org/10.1038/s41598-017-06158-3
PubMed:View item in PubMed

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