학술논문
Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
Document Type
article
Author
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
Source
Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
Subject
Language
English
ISSN
2045-2322
Abstract
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.