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Jäger, Susanne; Wahl, Simone; Kröger, Janine; Sharma, Sapna; Hoffmann, Per; Flögel, Anna; Pischon, Tobias; Prehn, Cornelia; Adamski, Jerzy; Müller-Nurasyid, Martina; Waldenberger, Melanie; Strauch, Konstantin; Peters, Annette; Gieger, Christian; Suhre, Karsten; Grallert, Harald; Böing, Heiner; Schulze, Matthias B.; Meidtner, Karina (2017): Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes. In: Scientific Reports, Vol. 7, 6037
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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.