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A robust method to estimate regional polygenic correlation under misspecified linkage disequilibrium structure
Guillaume Paré1,2,3, Shihong Mao1, Wei Q Deng4
1Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada.
Genetic Epidemiology
|August 30, 2018
Summary
Complex traits share genetic heritability, but this can vary across genomic regions. A new method, regional polygenic correlation (RPC), reveals this heterogeneity, offering insights into trait relationships like coronary artery disease.
Area of Science:
- Genetics
- Complex Trait Genetics
- Statistical Genetics
Background:
- Complex traits frequently share polygenic heritability.
- Genome-wide polygenic correlations can obscure locus-specific variations in shared genetic effects.
Purpose of the Study:
- To introduce a novel method for evaluating regional polygenic correlation (RPC) between complex traits.
- To identify heterogeneity in shared polygenic heritability across genomic loci.
Main Methods:
- Developed weighted maximum likelihood-based regional polygenic correlation (RPC) using summary association statistics.
- Assessed method calibration, power, and robustness to linkage disequilibrium misspecification via simulations.
- Applied RPC to cardiometabolic traits, including high-density lipoprotein cholesterol, coronary artery disease, and triglycerides metabolism.
Main Results:
- The RPC method is well-calibrated, powerful, and robust.
- Demonstrated significant heterogeneity in shared heritability across genomic regions for complex traits.
- Provided insights into the relationship between high-density lipoprotein cholesterol and coronary artery disease, implicating triglycerides metabolism.
Conclusions:
- Shared heritability between complex traits is not uniform but highly heterogeneous across genomic loci.
- RPC is a valuable tool for dissecting locus-specific genetic correlations and understanding complex trait etiology.
- Findings support further investigation into triglycerides metabolism and PPARγ activators for coronary artery disease prevention.
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