Juliá, AntonioGonzález, IsidoroFernández-Nebro, AntonioBlanco García, Francisco JRodríguez-Rodríguez, LuisGonzález, AntonioCañete, Juan D.Maymó, JoanAlperi-López, MercedesOlivé, AlexCorominas, HéctorMartínez-Taboada, VíctorErra, AlbaSánchez-Fernández, SimónAlonso, ArnaldLópez Lasanta, MaríaTortosa, RaülCodó, LaiaGelpi, Josep LluisGarcía-Montero, Andrés C.Bertranpetit, JaumeAbsher, Devin M.Bridges, S. LouisMyers, Richard M.Tornero, JesúsMarsal, Sara2026-05-042026-05-042016-03-15Julià A, González I, Fernández-Nebro A, Blanco F, Rodriguez L, González A, Cañete JD, Maymó J, Alperi-López M, Olivé A, Corominas H, Martínez-Taboada V, Erra A, Sánchez-Fernández S, Alonso A, Lopez-Lasanta M, Tortosa R, Codó L, Gelpi JL, García-Montero AC, Bertranpetit J, Absher D, Bridges SL Jr, Myers RM, Tornero J, Marsal S. A genome-wide association study identifies SLC8A3 as a susceptibility locus for ACPA-positive rheumatoid arthritis. Rheumatology (Oxford). 2016 Jun;55(6):1106-11.1462-0332https://hdl.handle.net/2183/48157[Abstract] Objective: RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach. Methods: A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry. Results: In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P < 5×10(-4) and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19×10(-8)]. Conclusions: SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants.engThis is a pre-copyedited, author-produced version of an article accepted for publication in Rheumatology following peer review. The version of record is available online on the OUP website.Anti-citrullinated protein antibodiesGenetic riskGenome-wide association studyJoint erosionsRheumatoid arthritisjournal articleopen access10.1093/RHEUMATOLOGY/KEW035