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Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

Bentham, James, Morris, David L, Cunninghame Graham, Deborah S, Pinder, Christopher L, Tombleson, Philip, Behrens, Timothy W, Martín, Javier, Fairfax, Benjamin P, Knight, Julian C, Chen, Lingyan, and others. (2015) Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nature Genetics, 47 (12). pp. 1457-1464. ISSN 1061-4036. (doi:10.1038/ng.3434)

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Abstract

Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry, constituting a new GWAS, a meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including ten new associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n = 16) of transcription factors among SLE susceptibility genes. This finding supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE.

Item Type: Article
DOI/Identification number: 10.1038/ng.3434
Uncontrolled keywords: Genome-wide association studies Systemic lupus erythematosus
Divisions: Faculties > Sciences > School of Mathematics Statistics and Actuarial Science
Faculties > Sciences > School of Mathematics Statistics and Actuarial Science > Statistics
Depositing User: James Bentham
Date Deposited: 16 Oct 2017 12:44 UTC
Last Modified: 29 May 2019 19:42 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/64033 (The current URI for this page, for reference purposes)
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