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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0abb98fcb66d4e54a7531e7e047fa972
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spelling	oai:doaj.org-article:0abb98fcb66d4e54a7531e7e047fa9722021-12-02T11:41:22ZGenetic variants including markers from the exome chip and metabolite traits of type 2 diabetes10.1038/s41598-017-06158-32045-2322https://doaj.org/article/0abb98fcb66d4e54a7531e7e047fa9722017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06158-3https://doaj.org/toc/2045-2322Abstract 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.Susanne JägerSimone WahlJanine KrögerSapna SharmaPer HoffmannAnna FloegelTobias PischonCornelia PrehnJerzy AdamskiMartina Müller-NurasyidMelanie WaldenbergerKonstantin StrauchAnnette PetersChristian GiegerKarsten SuhreHarald GrallertHeiner BoeingMatthias B. SchulzeKarina MeidtnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
description	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.
format	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
author_facet	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
author_sort	Susanne Jäger
title	Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
title_short	Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
title_full	Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
title_fullStr	Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
title_full_unstemmed	Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
title_sort	genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0abb98fcb66d4e54a7531e7e047fa972
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Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes

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