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Genome-wide association study identifies multiple loci influencing human serum metabolite levels
Authors:Kettunen Johannes  Tukiainen Taru  Sarin Antti-Pekka  Ortega-Alonso Alfredo  Tikkanen Emmi  Lyytikäinen Leo-Pekka  Kangas Antti J  Soininen Pasi  Würtz Peter  Silander Kaisa  Dick Danielle M  Rose Richard J  Savolainen Markku J  Viikari Jorma  Kähönen Mika  Lehtimäki Terho  Pietiläinen Kirsi H  Inouye Michael  McCarthy Mark I  Jula Antti  Eriksson Johan  Raitakari Olli T  Salomaa Veikko  Kaprio Jaakko  Järvelin Marjo-Riitta  Peltonen Leena  Perola Markus  Freimer Nelson B  Ala-Korpela Mika  Palotie Aarno  Ripatti Samuli
Institution:Institute for Molecular Medicine Finland, University of Helsinki, Finland.
Abstract:Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10(-10)) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders.
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