Genome-wide association study identifies multiple loci influencing human serum metabolite levels
- 29 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 44 (3), 269-276
- https://doi.org/10.1038/ng.1073
Abstract
Samuli Ripatti and colleagues report a genome-wide association study for human serum metabolites using NMR of serum samples from over 8,000 Finnish individuals. They identify 31 loci associated with at least one of 216 serum metabolic measures. 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.Keywords
This publication has 44 references indexed in Scilit:
- Gene Expression in Skin and Lymphoblastoid Cells: Refined Statistical Method Reveals Extensive Overlap in cis-eQTL SignalsAmerican Journal of Human Genetics, 2010
- MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypesGenetic Epidemiology, 2010
- A map of human genome variation from population-scale sequencingNature, 2010
- Integrating common and rare genetic variation in diverse human populationsNature, 2010
- Biological, clinical and population relevance of 95 loci for blood lipidsNature, 2010
- Variants in MTNR1B influence fasting glucose levelsNature Genetics, 2008
- Loci influencing lipid levels and coronary heart disease risk in 16 European population cohortsNature Genetics, 2008
- Genome-wide Association Study Identifies Genes for Biomarkers of Cardiovascular Disease: Serum Urate and DyslipidemiaAmerican Journal of Human Genetics, 2008
- A new multipoint method for genome-wide association studies by imputation of genotypesNature Genetics, 2007
- Heritabilities, apolipoprotein E, and effects of inbreeding on plasma lipids in a genetically isolated population: The Erasmus Rucphen Family StudyEuropean Journal of Epidemiology, 2007