A spectrum of recessiveness among Mendelian disease variants in UK Biobank.

ABSTRACT: Recent work has found increasing evidence of mitigated, incompletely penetrant phenotypes in heterozygous carriers of recessive Mendelian disease variants. We leveraged whole-exome imputation within the full UK Biobank cohort (n ∼ 500K) to extend such analyses to 3,475 rare variants curated from ClinVar and OMIM. Testing these variants for association with 58 quantitative traits yielded 102 significant associations involving variants previously implicated in 34 different diseases. Notable examples included a POR missense variant implicated in Antley-Bixler syndrome that associated with a 1.76 (SE 0.27) cm increase in height and an ABCA3 missense variant implicated in interstitial lung disease that associated with reduced FEV1/FVC ratio. Association analyses with 1,134 disease traits yielde

SUBMITTER: Barton AR 

PROVIDER: S-EPMC9300759 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature