Literature DB >> 22286219

Genome-wide association study identifies multiple loci influencing human serum metabolite levels.

Johannes Kettunen1, Taru Tukiainen, Antti-Pekka Sarin, Alfredo Ortega-Alonso, Emmi Tikkanen, Leo-Pekka Lyytikäinen, Antti J Kangas, Pasi Soininen, Peter Würtz, Kaisa Silander, Danielle M Dick, Richard J Rose, Markku J Savolainen, Jorma Viikari, Mika Kähönen, Terho Lehtimäki, Kirsi H Pietiläinen, Michael Inouye, Mark I McCarthy, Antti Jula, Johan Eriksson, Olli T Raitakari, Veikko Salomaa, Jaakko Kaprio, Marjo-Riitta Järvelin, Leena Peltonen, Markus Perola, Nelson B Freimer, Mika Ala-Korpela, Aarno Palotie, Samuli Ripatti.   

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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Year:  2012        PMID: 22286219      PMCID: PMC3605033          DOI: 10.1038/ng.1073

Source DB:  PubMed          Journal:  Nat Genet        ISSN: 1061-4036            Impact factor:   38.330


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