Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation.

ABSTRACT: Many multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identified; however, approximately half of MS heritability remains unexplained. We studied seven multiplex MS families, six of which with parental consanguinity, to identify genetic factors that increase MS risk. Candidate genomic regions were identified through linkage analysis and homozygosity mapping, and fully penetrant, rare, and low-frequency variants were detected by exome sequencing. Weighted sum score and polygenic risk score (PRS) analyses were conducted in MS families (24 affected, 17 unaffected), 23 sporadic MS cases, 63 individuals in 19 non-MS control families, and 1272 independent, ancestry-matched controls. We found that familial MS cases had a signifi

SUBMITTER: Everest E 

PROVIDER: S-EPMC9550807 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature