| Title: | Improved estimation of functional enrichment in SNP heritability using feasible generalized least squares |
| Journal: | Human Genetics and Genomics Advances |
| Published: | 7 Feb 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38327050/ |
| DOI: | https://doi.org/10.1016/j.xhgg.2024.100272 |
Publication 8773
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Abstract
Functional enrichment results typically implicate tissue or cell-type-specific biological pathways in disease pathogenesis and as therapeutic targets. We propose generalized linkage disequilibrium score regression (g-LDSC) that requires only genome-wide association studies (GWASs) summary-level data to estimate functional enrichment. The method adopts the same assumptions and regression model formulation as stratified linkage disequilibrium score regression (s-LDSC). Although s-LDSC only partially uses LD information, our method uses the whole LD matrix, which accounts for possible correlated error structure via a feasible generalized least-squares estimation. We demonstrate through simulation studies under various scenarios that g-LDSC provides more precise estimates of functional enrichment than s-LDSC, regardless of model misspecification. In an application to GWAS summary statistics of 15 traits from the UK Biobank, estimates of functional enrichment using g-LDSC were lower and more realistic than those obtained from s-LDSC. In addition, g-LDSC detected more significantly enriched functional annotations among 24 functional annotations for the 15 traits than s-LDSC (118 vs. 51).</p>
4 Authors
- Zewei Xiong
- Thuan-Quoc Thach
- Yan Dora Zhang
- Pak Chung Sham
1 Application
| Application ID | Title |
|---|---|
| 28732 | Novel methods for understanding of the genetic architecture of common diseases and traits |
Enabling scientific discoveries that improve human health