| Title: | SNP-to-gene linking strategies reveal contributions of enhancer-related and candidate master-regulator genes to autoimmune disease |
| Journal: | Cell Genomics |
| Published: | 13 Jul 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35873673/ |
| DOI: | https://doi.org/10.1016/j.xgen.2022.100145 |
| Citations: | 23 (18 in last 2 years) as of 8 Aug 2024 |
Publication 12306
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Abstract
We assess contributions to autoimmune disease of genes whose regulation is driven by enhancer regions (enhancer-related) and genes that regulate other genes in trans (candidate master-regulator). We link these genes to SNPs using several SNP-to-gene (S2G) strategies and apply heritability analyses to draw three conclusions about 11 autoimmune/blood-related diseases/traits. First, several characterizations of enhancer-related genes using functional genomics data are informative for autoimmune disease heritability after conditioning on a broad set of regulatory annotations. Second, candidate master-regulator genes defined using trans-eQTL in blood are also conditionally informative for autoimmune disease heritability. Third, integrating enhancer-related and master-regulator gene sets with protein-protein interaction (PPI) network information magnified their disease signal. The resulting PPI-enhancer gene score produced >2-fold stronger heritability signal and >2-fold stronger enrichment for drug targets, compared with the recently proposed enhancer domain score. In each case, functionally informed S2G strategies produced 4.1- to 13-fold stronger disease signals than conventional window-based strategies.</p>
7 Authors
- Kushal K. Dey
- Steven Gazal
- Bryce van de Geijn
- Samuel Sungil Kim
- Joseph Nasser
- Jesse M. Engreitz
- Alkes L. Price
1 Application
| Application ID | Title |
|---|---|
| 16549 | Components of heritability in a UK Biobank cohort |
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