Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
Kettunen J., Tukiainen T., Sarin A-P., Ortega-Alonso A., Tikkanen E., Lyytikäinen L-P., Kangas AJ., Soininen P., Würtz P., Silander K., Dick DM., Rose RJ., Savolainen MJ., Viikari J., Kähönen M., Lehtimäki T., Pietiläinen KH., Inouye M., McCarthy MI., Jula A., Eriksson J., Raitakari OT., Salomaa V., Kaprio J., Järvelin M-R., Peltonen L., Perola M., Freimer NB., Ala-Korpela M., Palotie A., Ripatti S.
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.