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

Fingerprint

Exome
Type 2 Diabetes Mellitus
Genes
Hexoses
Metabolomics
Phosphatidylcholines
Single Nucleotide Polymorphism
Meta-Analysis

ASJC Scopus subject areas

  • General

Cite this

Jäger, S., Wahl, S., Kröger, J., Sharma, S., Hoffmann, P., Floegel, A., ... 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

Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes. / Jäger, Susanne; Wahl, Simone; Kröger, Janine; Sharma, Sapna; Hoffmann, Per; Floegel, Anna; Pischon, Tobias; Prehn, Cornelia; Adamski, Jerzy; Müller-Nurasyid, Martina; Waldenberger, Melanie; Strauch, Konstantin; Peters, Annette; Gieger, Christian; Suhre, Karsten; Grallert, Harald; Boeing, Heiner; Schulze, Matthias B.; Meidtner, Karina.

In: Scientific Reports, Vol. 7, No. 1, 6037, 01.12.2017.

Research output: Contribution to journalArticle

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, MB & Meidtner, K 2017, 'Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes', Scientific Reports, vol. 7, no. 1, 6037. https://doi.org/10.1038/s41598-017-06158-3
Jäger, Susanne ; Wahl, Simone ; Kröger, Janine ; Sharma, Sapna ; Hoffmann, Per ; Floegel, Anna ; Pischon, Tobias ; Prehn, Cornelia ; Adamski, Jerzy ; Müller-Nurasyid, Martina ; Waldenberger, Melanie ; Strauch, Konstantin ; Peters, Annette ; Gieger, Christian ; Suhre, Karsten ; Grallert, Harald ; Boeing, Heiner ; Schulze, Matthias B. ; Meidtner, Karina. / Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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