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Title: Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus
Author: Julià, Antonio
López Longo, Francisco J.
Pérez Venegas, José Javier
Bonàs Guarch, Sílvia
Olivé Marqués, Alejandro
Andreu, José Luis
Aguirre Zamorano, Mª. Ángeles
Vela, Paloma
Nolla i Salas, Joan
Marenco de la Fuente, José Luís
Zea, Antonio
Pego Reigosa, José María
Freire, Mercedes
Díez, Elvira
Rodríguez Almaraz, Esther
Carreira, Patricia
Blanco, Ricardo
Martínez Taboada, Víctor Manuel
López Lasanta, María
López Corbeto, Mireia
Mercader, Josep M.
Torrents Arenales, David
Absher, Devin
Marsal Barril, Sara
Fernández Nebro, Antonio
Keywords: Lupus eritematós
Malalties de la pell
Malalties autoimmunitàries
Genoma humà
Lupus erythematosus
Skin diseases
Autoimmune diseases
Human genome
Issue Date: 30-May-2018
Publisher: BioMed Central
Abstract: BACKGROUND: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. METHODS: We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. RESULTS: We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10- 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10- 6), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10- 5), interleukin-4 signaling (p = 3.97 × 10- 5) and cell surface interactions at the vascular wall (p = 4.63 × 10- 5). CONCLUSIONS: Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci.
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It is part of: Arthritis Research & Therapy, 2018, vol. 20, num. 1, p. 100
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ISSN: 1478-6362
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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