Ultra-rare complement factor 8 coding variants in families with age-related macular degeneration.

ABSTRACT: Genome-wide association studies have uncovered 52 independent common and rare variants across 34 genetic loci, which influence susceptibility to age related macular degeneration (AMD). Of the 5 AMD-associated complement genes, complement factor H (CFH) and CFI exhibit a significant rare variant burden implicating a major contribution of the complement pathway to disease pathology. However, the efforts for developing AMD therapy have been challenging as of yet. Here, we report the identification of ultra-rare variants in complement factors 8A and 8B, two components of the terminal complement membrane attack complex (MAC), by whole exome sequencing of a cohort of AMD families. The identified C8 variants impact local interactions among proteins of C8 triplex in vitro, indicating their

SUBMITTER: Zelinger L 

PROVIDER: S-EPMC10156737 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature