| Title: | Integration of expression QTLs with fine mapping via SuSiE. |
| Journal: | PLOS Genetics |
| Published: | 25 Jan 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38271473/ |
| DOI: | https://doi.org/10.1371/journal.pgen.1010929 |
| URL: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010929&type=printable |
Publication 8865
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Genome-wide association studies (GWASs) have achieved remarkable success in associating thousands of genetic variants with complex traits. However, the presence of linkage disequilibrium (LD) makes it challenging to identify the causal variants. To address this critical gap from association to causation, many fine-mapping methods have been proposed to assign well-calibrated probabilities of causality to candidate variants, taking into account the underlying LD pattern. In this manuscript, we introduce a statistical framework that incorporates expression quantitative trait locus (eQTL) information to fine-mapping, built on the sum of single-effects (SuSiE) regression model. Our new method, SuSiE2, connects two SuSiE models, one for eQTL analysis and one for genetic fine-mapping. This is achieved by first computing the posterior inclusion probabilities (PIPs) from an eQTL-based SuSiE model with the expression level of the candidate gene as the phenotype. These calculated PIPs are then utilized as prior inclusion probabilities for risk variants in another SuSiE model for the trait of interest. By prioritizing functional variants within the candidate region using eQTL information, SuSiE2 improves SuSiE by increasing the detection rate of causal SNPs and reducing the average size of credible sets. We compared the performance of SuSiE2 with other multi-trait fine-mapping methods with respect to power, coverage, and precision through simulations and applications to the GWAS results of Alzheimer's disease (AD) and body mass index (BMI). Our results demonstrate the better performance of SuSiE2, both when the in-sample linkage disequilibrium (LD) matrix and an external reference panel is used in inference.</p>
3 Authors
- Xiangyu Zhang
- Wei Jiang
- Hongyu Zhao
1 Application
| Application ID | Title |
|---|---|
| 29900 | Defining physical activity phenotypes based on objective measures and dissecting the genetic and phenotypic relationships of physical activity with diseases and health outcomes |
Enabling scientific discoveries that improve human health