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2018-05-30

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cc-by (c) Julià, Antonio et al., 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/132989

Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus

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https://doi.org/10.1186/s13075-018-1604-1

Resum

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.

Matèries

Lupus eritematós, Malalties de la pell, Malalties autoimmunitàries, Genoma humà

Matèries (anglès)

Lupus erythematosus, Skin diseases, Autoimmune diseases, Human genome

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Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

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 SOLÉ, Joan miquel, MARENCO DE LA FUENTE, José luis, 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. Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus. _Arthritis Research & Therapy_. 2018. Vol. 20, núm. 1, pàgs. 100. [consulta: 27 de gener de 2026]. ISSN: 1478-6362. [Disponible a: https://hdl.handle.net/2445/132989]

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