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 language | English |
|---|---|
| Article number | 6037 |
| Journal | Scientific Reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
AU - Jäger, Susanne
AU - Wahl, Simone
AU - Kröger, Janine
AU - Sharma, Sapna
AU - Hoffmann, Per
AU - Floegel, Anna
AU - Pischon, Tobias
AU - Prehn, Cornelia
AU - Adamski, Jerzy
AU - Müller-Nurasyid, Martina
AU - Waldenberger, Melanie
AU - Strauch, Konstantin
AU - Peters, Annette
AU - Gieger, Christian
AU - Suhre, Karsten
AU - Grallert, Harald
AU - Boeing, Heiner
AU - Schulze, Matthias B.
AU - Meidtner, Karina
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85025462539&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85025462539&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-06158-3
DO - 10.1038/s41598-017-06158-3
M3 - Article
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 6037
ER -