Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple - even distinct - traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10-8) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10-7) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes.
|Number of pages||16|
|Journal||American Journal of Human Genetics|
|State||Published - Jan 8 2015|
Bibliographical noteFunding Information:
We are gratefully indebted to Robert C. Elston for his valuable discussions and suggestions that greatly improved the manuscript. The work was supported by the NIH grants HG003054 from the National Human Genome Research Institute and HL086718, HL053353, HL113338, and HL123677 from the National Heart, Lung, and Blood Institute. Funding information for the COGENT BP Consortium is provided in the Supplemental Data .
© 2015 The American Society of Human Genetics.
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