Background Recent genome-wide association studies (GWAS) have identified more than 50 loci associated with systemic lupus erythematosus but they explain less than 30% of the heritability of the disease. Meta-analysis including new populations can contribute to identify additional genetic risk factors.
Objectives The aim of the presents study was to identify additional genetic risk loci for SLE.
Methods We performed a meta-analysis using data from a recent large scale GWAS from 4,036 cases and 6,959 controls from Caucasian European ancestry  and a newly genotyped cohort of 907 SLE patients and 1,524healthy controls from Spain. Genetic association was tested at the single-marker level using linear regression and at the pathway-level using Fisher's modified method.
Results Combining the two cohorts we identified genome-wide significant association (P<5E-8) at five new loci: three SNPs at intragenic regions and two intergenic loci at chromosomes 7q11.23 (Manhattan plot for chromosome 7 is shown in Figure; new SLE risk region SNPs highlighted in green) and 17q21.31. Several of the new associated genes are functionally associated with B cell regulation. After multiple test correction, B Cell Receptor signaling, Biopeptides and Cell surface interactions at the vascular wall pathways were also significantly associated with SLE risk.
Conclusions In conclusion, we have identified five new risk loci for SLE through a meta-analysis including a new GWAS.
Bentham J, Morris DL et al. Nature Genetics 2015.
Acknowledgements We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaboration. We would also like to thank the international SLE consortium for access to the data.
Disclosure of Interest None declared
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