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) (KAR id:64033)
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| Official URL: https://doi.org/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 |
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| DOI/Identification number: | 10.1038/ng.3434 |
| Uncontrolled keywords: | Genome-wide association studies Systemic lupus erythematosus |
| Subjects: |
Q Science > QA Mathematics (inc Computing science) > QA276 Mathematical statistics Q Science > QH Natural history > QH426 Genetics |
| Divisions: | Divisions > Division of Computing, Engineering and Mathematical Sciences > School of Mathematics, Statistics and Actuarial Science |
| Depositing User: | James Bentham |
| Date Deposited: | 16 Oct 2017 12:44 UTC |
| Last Modified: | 05 Nov 2024 11:00 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/64033 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Bentham, James.
| Creator's ORCID: |
 https://orcid.org/0000-0001-5733-9417
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