TY - JOUR T1 - Fine-mapping identifies causal variants for RA and T1D in <em>DNASE1L3, SIRPG, MEG3, TNFAIP3</em> and <em>CD28/CTLA4</em> loci JF - bioRxiv DO - 10.1101/151423 SP - 151423 AU - Harm-Jan Westra AU - Marta Martinez Bonet AU - Suna Onengut AU - Annette Lee AU - Yang Luo AU - Nick Teslovich AU - Jane Worthington AU - Javier Martin AU - Tom Huizinga AU - Lars Klareskog AU - Solbritt Rantapaa-Dahlqvist AU - Wei-Min Chen AU - Aaron Quinlan AU - John A. Todd AU - Steve Eyre AU - Peter A. Nigrovic AU - Peter K. Gregersen AU - Stephen S Rich AU - Soumya Raychaudhuri Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/19/151423.abstract N2 - We fine-mapped 76 rheumatoid arthritis (RA) and type 1 diabetes (T1D) loci outside of the MHC. After sequencing 799 1kb regulatory (H3K4me3) regions within these loci in 568 individuals, we observed accurate imputation for 89% of common variants. We fine-mapped1,2 these loci in RA (11,475 cases, 15,870 controls)3, T1D (9,334 cases and 11,111 controls) 4 and combined datasets. We reduced the number of potential causal variants to ≤5 in 8 RA and 11 T1D loci. We identified causal missense variants in five loci (DNASE1L3, SIRPG, PTPN22, SH2B3 and TYK2) and likely causal non-coding variants in six loci (MEG3, TNFAIP3, CD28/CTLA4, ANKRD55, IL2RA, REL/PUS10). Functional analysis confirmed allele specific binding and differential enhancer activity for three variants: the CD28/CTLA4 rs117701653 SNP, the TNFAIP3 rs35926684 indel, and the MEG3 rs34552516 indel. This study demonstrates the potential for dense genotyping and imputation to pinpoint missense and non-coding causal alleles. ER -