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

Susanne Jäger, Simone Wahl, Janine Kröger, Sapna Sharma, Per Hoffmann, Anna Floegel, Tobias Pischon, Cornelia Prehn, Jerzy Adamski, Martina Müller-Nurasyid, Melanie Waldenberger, Konstantin Strauch, Annette Peters, Christian Gieger, Karsten Suhre, Harald Grallert, Heiner Boeing, Matthias B. Schulze, Karina Meidtner

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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.

Original languageEnglish
Article number6037
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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Cite this

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. (2017). Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes. Scientific Reports, 7(1), [6037]. https://doi.org/10.1038/s41598-017-06158-3