López-Mejías, RaquelCarmona, F DavidGenre, FernandaRemuzgo-Martínez, SaraGonzález-Juanatey, CarlosCorrales, AlfonsoVicente, Esther FPulito-Cueto, VerónicaMiranda-Filloy, José ARamírez Huaranga, Marco ABlanco, RicardoRobustillo-Villarino, MontserratRodríguez-Carrio, JavierAlperi-López, MercedesAlegre-Sancho, Juan JMijares, VerónicaLera-Gómez, LeticiaPérez-Pampín, EvaGonzález, AntonioOrtega-Castro, RafaelaLópez-Pedrera, CharyGarcía Vivar, Mari LGómez-Arango, CatalinaRaya, EnriqueNarvaez, JavierBalsa, AlejandroLópez-Longo, Francisco JCarreira, PatriciaGonzález-Álvaro, IsidoroRodríguez-Rodríguez, LuisFernández-Gutiérrez, BenjamínFerraz-Amaro, IvánGualillo, OresteCastañeda, SantosMartín, JavierLlorca, JavierGonzález-Gay, Miguel A2023-01-252023-01-252019-01-18http://hdl.handle.net/10668/12993To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). We performed a genome-wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima-media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals. A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome-wide level of significance (minor allele [G] β coefficient 0.142, P = 1.86 × 10-8 ). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate-adjusted P = 4.01 × 10-3 ). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1, MSRA, and ZC3HC1 (P = 8.12 × 10-4 , P = 5.94 × 10-4 , and P = 2.46 × 10-4 , respectively). The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/3' Untranslated RegionsAdaptor Proteins, Signal TransducingAdultArthritis, RheumatoidAtherosclerosisCarotid ArteriesCarotid Intima-Media ThicknessCell Cycle ProteinsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMethionine Sulfoxide ReductasesMiddle AgedNF-kappa B p50 SubunitNuclear ProteinsReceptors, Retinoic AcidRisk Factorsresearch article30251476open access10.1002/art.407342326-5205PMC6590191https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.40734https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590191/pdf