Whole-Exome Sequencing Improves Risk Assessments of Adult Moyamoya Disease

Background and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition.Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD.Methods This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores.Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES.Mutant-allele risk scores (MARSs) were created based on WESidentified mutations.Gene-based association analyses and pooled analyses in East-Asian populations were further performed.Results Fourteen mutations reached the genome-wide significance criterion (p