| Title: |
Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features |
| Authors: |
Ray, John P; de Boer, Carl G; Fulco, Charles P; Lareau, Caleb A; Kanai, Masahiro; Ulirsch, Jacob C; Tewhey, Ryan; Ludwig, Leif S; Reilly, Steven K; Bergman, Drew T; Engreitz, Jesse M; Issner, Robbyn; Finucane, Hilary K; Lander, Eric S; Regev, Aviv; Hacohen, Nir |
| Contributors: |
Massachusetts Institute of Technology. Department of Biology |
| Source: |
Nature |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2021 |
| Collection: |
DSpace@MIT (Massachusetts Institute of Technology) |
| Description: |
Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associated variants are enriched among SNPs prioritized based on either: (1) residing within CRISPRi-sensitive regulatory regions, or (2) localizing in a chromatin accessible region while displaying allele-specific reporter activity. Of the 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both of these criteria, 5 of which are further supported by genetic fine-mapping. Our work provides a comprehensive strategy to characterize genetic variation at important disease-associated loci, and aids in the effort to identify trait causal genetic variants. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Nature Communications; https://hdl.handle.net/1721.1/136246 |
| Availability: |
https://hdl.handle.net/1721.1/136246 |
| Rights: |
Creative Commons Attribution 4.0 International license ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.9EAA0CDC |
| Database: |
BASE |