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

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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Arthritis Res Ther. 2018 May 30;20(1):100.

Editorial: BioMed Central

 Fecha de publicación: 01/05/2018

Nº de páginas: 10

Tipo de publicación: Artículo de Revista

 DOI: 10.1186/s13075-018-1604-1

ISSN: 1478-6354,1478-6362

Url de la publicación: https://doi.org/10.1186/s13075-018-1604-1

Autores/as

JULIÀ, ANTONIO

LÓPEZ LONGO, FRANCISCO JAVIER

PÉREZ VENEGAS, JOSÉ J.

BONÀS GUARCH, SILVIA

OLIVÉ, ÀLEX

ANDREU, JOSÉ LUÍS

AGUIRRE ZAMORANO, Mª. ÁNGELES

VELA, PALOMA

NOLLA, JOAN M.

MARENCO DE LA FUENTE, JOSÉ LUÍS

ZEA, ANTONIO

PEGO REIGOSA, JOSÉ MARÍA

FREIRE, MERCEDES

DÍEZ, ELVIRA

RODRÍGUEZ ALMARAZ, ESTHER

CARREIRA, PATRICIA

RICARDO BLANCO ALONSO

LÓPEZ LASANTA, MARÍA

LÓPEZ CORBETO, MIREIA