Discovery and Functional Characterization of Two Regulatory Variants Underlying Lupus Susceptibility at 2p13.1.

ABSTRACT: Genome-wide association studies have identified 2p13.1 as a prominent susceptibility locus for systemic lupus erythematosus (SLE)—a complex, multisystem autoimmune disease. However, the identity of underlying causal variant (s) and molecular mechanisms for increasing disease susceptibility are poorly understood. Using meta-analysis (cases = 10,252, controls = 21,604) followed by conditional analysis, bioinformatic annotation, and eQTL and 3D-chromatin interaction analyses, we computationally prioritized potential functional variants and subsequently experimentally validated their effects. Ethnicity-specific meta-analysis revealed striking allele frequency differences between Asian and European ancestries, but with similar odds ratios. We identified 20 genome-wide significant (p < 5 × 10−8)

SUBMITTER: Fazel-Najafabadi M 

PROVIDER: S-EPMC9222795 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature