| Title: | Localizing Components of Shared Transethnic Genetic Architecture of Complex Traits from GWAS Summary Data |
| Journal: | American Journal of Human Genetics |
| Published: | 21 May 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32442408/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2020.04.012 |
| URL: | http://www.cell.com/article/S000292972030121X/pdf |
| Citations: | 81 (31 in last 2 years) as of 8 Aug 2024 |
Publication 9115
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Abstract
Despite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations suggests the presence of population-specific components of genetic architecture. We propose an approach that models GWAS summary data for one trait in two populations to estimate genome-wide proportions of population-specific/shared causal SNPs. In simulations across various genetic architectures, we show that our approach yields approximately unbiased estimates with in-sample LD and slight upward-bias with out-of-sample LD. We analyze nine complex traits in individuals of East Asian and European ancestry, restricting to common SNPs (MAF > 5%), and find that most common causal SNPs are shared by both populations. Using the genome-wide estimates as priors in an empirical Bayes framework, we perform fine-mapping and observe that high-posterior SNPs (for both the population-specific and shared causal configurations) have highly correlated effects in East Asians and Europeans. In population-specific GWAS risk regions, we observe a 2.8× enrichment of shared high-posterior SNPs, suggesting that population-specific GWAS risk regions harbor shared causal SNPs that are undetected in the other GWASs due to differences in LD, allele frequencies, and/or sample size. Finally, we report enrichments of shared high-posterior SNPs in 53 tissue-specific functional categories and find evidence that SNP-heritability enrichments are driven largely by many low-effect common SNPs.</p>
9 Authors
- Huwenbo Shi
- Kathryn S Burch
- Ruth Johnson
- Malika K Freund
- Gleb Kichaev
- Nicholas Mancuso
- Astrid M Manuel
- Natalie Dong
- Bogdan Pasaniuc
1 Application
| Application ID | Title |
|---|---|
| 33297 | Quantifying the role of linkage disequilibrium in mapping genetic regions within and across traits. |
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