![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
![[thumbnail of Supplementary Information]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Information)
16MB |
| Item Type: | Article |
|---|---|
| Title: | Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features |
| Creators Name: | Ray, J.P., de Boer, C.G., Fulco, C.P., Lareau, C.A., Kanai, M., Ulirsch, J.C., Tewhey, R., Ludwig, L.S., Reilly, S.K., Bergman, D.T., Engreitz, J.M., Issner, R., Finucane, H.K., Lander, E.S., Regev, A. and Hacohen, N. |
| Abstract: | 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. |
| Keywords: | Autoimmune Diseases, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Haplotypes, Linkage Disequilibrium, Multifactorial Inheritance, Proof of Concept Study, Tumor Cell Line, Tumor Necrosis Factor alpha-Induced Protein 3 |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 11 |
| Number: | 1 |
| Page Range: | 1237 |
| Date: | 6 March 2020 |
| Official Publication: | https://doi.org/10.1038/s41467-020-15022-4 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
