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Jäger, S.* ; Wahl, S. ; Kröger, J.* ; Sharma, S. ; Hoffmann, P.* ; Floegel, A.* ; Pischon, T.* ; Prehn, C. ; Adamski, J. ; Müller-Nurasyid, M. ; Waldenberger, M. ; Strauch, K. ; Peters, A. ; Gieger, C. ; Suhre, K.* ; Grallert, H. ; Boeing, H.* ; Schulze, M.B.* ; Meidtner, K.*

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

Sci. Rep. 7:6037 (2017)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Genome-wide Association; Fasting Glucose; Low-frequency; Risk; Population; Link; Rare; Susceptibility; Cancer; Kora

ISSN (print) / ISBN 2045-2322

e-ISSN 2045-2322

Journal Scientific Reports

Quellenangaben Volume: 7, Issue: 1, Article Number: 6037

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Molekulare Endokrinologie und Metabolismus (MEM)