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
