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

Content Provider	Springer Nature : BioMed Central
Author	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
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.
Related Links	https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/s13075-018-1604-1.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14786362
DOI	10.1186/s13075-018-1604-1
Journal	Arthritis Research & Therapy
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2018-05-30
Access Restriction	Open
Subject Keyword	Rheumatology Orthopedics Systemic lupus erythematosus Genetic susceptibility Genome-wide association study Meta-analysis Biological pathway analysis
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology
Journal Impact Factor	4.4/2023
5-Year Journal Impact Factor	4.9/2023

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