Variation in CFHR3 determines susceptibility to meningococcal disease by controlling factor H concentrations.

ABSTRACT: Neisseria meningitidis protects itself from complement-mediated killing by binding complement factor H (FH). Previous studies associated susceptibility to meningococcal disease (MD) with variation in CFH, but the causal variants and underlying mechanism remained unknown. Here we attempted to define the association more accurately by sequencing the CFH-CFHR locus and imputing missing genotypes in previously obtained GWAS datasets of MD-affected individuals of European ancestry and matched controls. We identified a CFHR3 SNP that provides protection from MD (rs75703017, p value = 1.1 × 10^-16) by decreasing the concentration of FH in the blood (p value = 1.4 × 10^-11). We subsequently used dual-luciferase studies and CRISPR gene editing to establish that deletion of rs757

SUBMITTER: Kumar V 

PROVIDER: S-EPMC9502058 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature