Difference between revisions of "Total Explained Variance"
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<newstitle>Novel method to estimate explained variance of GWAS hits reveals large fraction of the missing heritability</newstitle> | <newstitle>Novel method to estimate explained variance of GWAS hits reveals large fraction of the missing heritability</newstitle> | ||
<teaser> | <teaser> | ||
| − | In collaboration with John Whittaker (GSK) we have published a new methodology to infer total explained variance of [[Genome Wide Association Studies | GWAS]] hits. Our method was applied to the most recent GIANT association summary statistics and revealed that GWAS hits explain at least 30% of human height variations. The article appeared online in | + | In collaboration with John Whittaker (GSK) we have published a new methodology to infer total explained variance of [[Genome Wide Association Studies | GWAS]] hits. Our method was applied to the most recent GIANT association summary statistics and revealed that GWAS hits explain at least 30% of human height variations. The article appeared online in <a href="http://onlinelibrary.wiley.com/doi/10.1002/gepi.20582/abstract;jsessionid=9C088B31B90307D9588A29394535DDDF.d03t01">Genetic Epidemiology</a> on 6 April 2011. |
<date>6 April 2011 — 21:35</date> | <date>6 April 2011 — 21:35</date> | ||
</teaser> | </teaser> | ||
Latest revision as of 16:07, 20 August 2012
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. For more details click here.
A simple Matlab package of the algorithm can be downloaded from here. Read, modify and launch the main.m file.
Kutalik Z, Whittaker J, Waterworth D, GIANT consortium, Beckmann JS, Bergmann S
Novel method to estimate the phenotypic variation explained by genome-wide association studies reveals large fraction of the missing heritability.
Genet Epidemiol: 2011 Jul, 35(5);341-9
[PubMed:21465548]
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