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

Sci Rep. 2017 Jul 20;7(1):6037. doi: 10.1038/s41598-017-06158-3.

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.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Biomarkers
  • Delta-5 Fatty Acid Desaturase
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Exome*
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genome-Wide Association Study
  • Humans
  • Metabolome*
  • Metabolomics* / methods
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis*
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Quantitative Trait, Heritable

Substances

  • Biomarkers
  • Delta-5 Fatty Acid Desaturase
  • FADS1 protein, human