A genome-wide association study identifies SLC8A3 as a susceptibility locus for ACPA-positive rheumatoid arthritis.
|Title||A genome-wide association study identifies SLC8A3 as a susceptibility locus for ACPA-positive rheumatoid arthritis.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Julià, Antonio, González Isidoro, Fernández-Nebro Antonio, Blanco Francisco, Rodriguez Luis, González Antonio, Cañete Juan D., Maymó Joan, Alperi-López Mercedes, Olivé Alejandro, Corominas Héctor, Martínez-Taboada Víctor, Erra Alba, Sánchez-Fernández Simón, Alonso Arnald, López-Lasanta María, Tortosa Raül, Codó Laia, Gelpí Josep-Lluis, García-Montero Andres C., Bertranpetit Jaume, Absher Devin, S Bridges Louis, Myers Richard M., Tornero Jesús, and Marsal Sara|
|Date Published||2016 Jun|
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)