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| Status |
Public on Feb 11, 2020 |
| Title |
Assessing the ability of various genomic features to prioritize causal non-coding variants associated with diseases and traits [MPRA] |
| Organisms |
Homo sapiens; unidentified plasmid |
| Experiment type |
Other
|
| Summary |
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 used seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in three disease-relevant immune cell types, based on a set of features related to regulatory potential. Trait/disease-associated variants were 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 had at least one variant meeting one or both of these criteria, with 3 of these haplotypes having a single prioritized variant. 5 of the 9 prioritized variants were further supported by genetic fine-mapping in our and other studies. Our work provides evidence for the efficacy and limitations of strategies for prioritizing disease- and trait-associated genetic variants.
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| Overall design |
Massively parallel reporter assays to study variant effects on reporter expression, 2-3 replicates, 3 cell types, 4 cell lines, lentiviral and transfection
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| Contributor(s) |
Ray JP, de Boer CG |
| Citation(s) |
32144282 |
| Submission date |
Aug 30, 2019 |
| Last update date |
Apr 01, 2020 |
| Contact name |
Carl G de Boer |
| Organization name |
The Broad Institute
|
| Lab |
Aviv Regev
|
| Street address |
415 Main St
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL25362 |
Illumina HiSeq 2500 (unidentified plasmid) |
|
| Samples (33)
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| This SubSeries is part of SuperSeries: |
| GSE136703 |
Assessing the ability of various genomic features to prioritize causal non-coding variants associated with diseases and traits |
|
| Relations |
| BioProject |
PRJNA563094 |
| SRA |
SRP219970 |
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