title: Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
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.
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.forename: Taru
authors.initials: T
authors.lastname: Tukiainen
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Sarin
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ortega-Alonso
authors.forename: Emmi
authors.initials: E
authors.lastname: Tikkanen
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.forename: Kaisa
authors.initials: K
authors.lastname: Silander
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rose
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.forename: Johan
authors.initials: J
authors.lastname: Eriksson
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Freimer
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D005387:Finland; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D044967:Serum / Q000378:metabolism*
chemical_list: D000596:Amino Acids