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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., 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. 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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