Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus
2015 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 12, 1457-1464 p.Article in journal, Letter (Refereed) Published
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.
Place, publisher, year, edition, pages
2015. Vol. 47, no 12, 1457-1464 p.
Immunology in the medical area Medical Genetics
IdentifiersURN: urn:nbn:se:uu:diva-269315DOI: 10.1038/ng.3434ISI: 000365813200018PubMedID: 26502338OAI: oai:DiVA.org:uu-269315DiVA: diva2:882663
FunderSwedish Research CouncilEU, European Research CouncilWellcome trust, 085492NIH (National Institute of Health), 3P50CA093459NIH (National Institute of Health), 5P50CA097007NIH (National Institute of Health), 5P50CA097007NIH (National Institute of Health), 5R01CA133996NIH (National Institute of Health), R37HL039693