Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus.

ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of multiple organ systems and dysregulated interferon responses. SLE is both genetically and phenotypically heterogeneous, greatly reducing the power of case-control studies in SLE. Elevated circulating interferon-alpha (IFN-α) is a stable, heritable trait in SLE, which has been implicated in primary disease pathogenesis. About 40-50% of patients have high IFN-α, and high levels correspond with clinical differences. To study genetic heterogeneity in SLE, we performed a case-case study comparing patients with high vs low IFN-α in over 1550 SLE cases, including genome-wide association study and replication cohorts. In meta-analysis, the top associations in European ancestry were protein kinase,

SUBMITTER: Kariuki SN 

PROVIDER: S-EPMC4305028 | biostudies-literature | 2015 Jan-Feb

REPOSITORIES: biostudies-literature