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

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...

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Authors: 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, de la Fuente, José Luís Marenco, Zea, Antonio, Pego-Reigosa, José María, Freire, Mercedes, Díez, Elvira, Rodríguez-Almaraz, Esther, Carreira, Patricia, Blanco, Ricardo, Taboada, Víctor Martínez, López-Lasanta, María, Corbeto, Mireia López, Mercader, Josep M, Torrents, David, Absher, Devin, Marsal, Sara, Fernández-Nebro, Antonio
Format: article
Publication Date:2018
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17600
Online Access:http://hdl.handle.net/20.500.12105/17600
Access Level:Open access
Keyword:Biological pathway analysis
Genetic susceptibility
Genome-wide association study
Meta-analysis
Systemic lupus erythematosus
Cohort Studies
Genetic Loci
Genetic Variation
Genome-Wide Association Study
Humans
Lupus Erythematosus, Systemic
Description
Summary: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. 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. We identified five new loci associated with SLE at the genome-wide level of significance (p  Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci.

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