Novel method to estimate the phenotypic variation explained by genome-wide association studies reveals large fraction of the missing heritability.

Details

Serval ID
serval:BIB_EE565D42F520
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Novel method to estimate the phenotypic variation explained by genome-wide association studies reveals large fraction of the missing heritability.
Journal
Genetic Epidemiology
Author(s)
Kutalik Z., Whittaker J., Waterworth D., Beckmann J.S., Bergmann S.
Working group(s)
GIANT consortium
ISSN
1098-2272 (Electronic)
ISSN-L
0741-0395
Publication state
Published
Issued date
2011
Volume
35
Number
5
Pages
341-349
Language
english
Abstract
Genome-wide association studies (GWAS) are conducted with the promise to discover novel genetic variants associated with diverse traits. For most traits, associated markers individually explain just a modest fraction of the phenotypic variation, but their number can well be in the hundreds. We developed a maximum likelihood method that allows us to infer the distribution of associated variants even when many of them were missed by chance. Compared to previous approaches, the novelty of our method is that it (a) does not require having an independent (unbiased) estimate of the effect sizes; (b) makes use of the complete distribution of P-values while allowing for the false discovery rate; (c) takes into account allelic heterogeneity and the SNP pruning strategy. We applied our method to the latest GWAS meta-analysis results of the GIANT consortium. It revealed that while the explained variance of genome-wide (GW) significant SNPs is around 1% for waist-hip ratio (WHR), the observed P-values provide evidence for the existence of variants explaining 10% (CI=[8.5-11.5%]) of the phenotypic variance in total. Similarly, the total explained variance likely to exist for height is estimated to be 29% (CI=[28-30%]), three times higher than what the observed GW significant SNPs give rise to. This methodology also enables us to predict the benefit of future GWA studies that aim to reveal more associated genetic markers via increased sample size.
Pubmed
Web of science
Create date
02/09/2011 18:08
Last modification date
20/08/2019 16:15
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