Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus
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Author
Bentham, James
Morris, David L
Graham, Deborah S Cunninghame
Pinder, Christopher L
Tombleson, Philip
Behrens, Timothy W
Martín, Javier
Fairfax, Benjamin P
Knight, Julian C
Chen, Lingyan
Replogle, Joseph
Syvänen, Ann-Christine
Rönnblom, Lars
Graham, Robert R
Wither, Joan E
Rioux, John D
Alarcón-Riquelme, Marta E
Vyse, Timothy J
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.3434Metadata
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Bentham, J., D. L. Morris, D. S. C. Graham, C. L. Pinder, P. Tombleson, T. W. Behrens, J. Martín, et al. 2015. “Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.” Nature genetics 47 (12): 1457-1464. doi:10.1038/ng.3434. http://dx.doi.org/10.1038/ng.3434.Abstract
Systemic lupus erythematosus (SLE; OMIM 152700) 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: a new GWAS, meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including 10 novel 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 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668589/pdf/Terms of Use
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