| Literature DB >> 30224649 |
Harm-Jan Westra1,2,3,4,5, Marta Martínez-Bonet4, Suna Onengut-Gumuscu6,7, Annette Lee8, Yang Luo1,2,3,4, Nikola Teslovich1,2,3,4, Jane Worthington9,10, Javier Martin11, Tom Huizinga12, Lars Klareskog13, Solbritt Rantapaa-Dahlqvist14, Wei-Min Chen6,7, Aaron Quinlan6,15,16, John A Todd17, Steve Eyre9,10, Peter A Nigrovic4,18, Peter K Gregersen8, Stephen S Rich6,7, Soumya Raychaudhuri19,20,21,22,23,24.
Abstract
To define potentially causal variants for autoimmune disease, we fine-mapped1,2 76 rheumatoid arthritis (11,475 cases, 15,870 controls)3 and type 1 diabetes loci (9,334 cases, 11,111 controls)4. After sequencing 799 1-kilobase regulatory (H3K4me3) regions within these loci in 568 individuals, we observed accurate imputation for 89% of common variants. We defined credible sets of ≤5 causal variants at 5 rheumatoid arthritis and 10 type 1 diabetes loci. We identified potentially causal missense variants at DNASE1L3, PTPN22, SH2B3, and TYK2, and noncoding variants at MEG3, CD28-CTLA4, and IL2RA. We also identified potential candidate causal variants at SIRPG and TNFAIP3. Using functional assays, we confirmed allele-specific protein binding and differential enhancer activity for three variants: the CD28-CTLA4 rs117701653 SNP, MEG3 rs34552516 indel, and TNFAIP3 rs35926684 indel.Entities:
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Year: 2018 PMID： 30224649 PMCID： PMC6364548 DOI： 10.1038/s41588-018-0216-7
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307