Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores.

ABSTRACT:

Background

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) is a congenital malformation of multifactorial etiology. Research has identified >40 genome-wide significant risk loci, which explain less than 40% of nsCL/P heritability. Studies show that some of the hidden heritability is explained by rare penetrant variants.

Methods

To identify new candidate genes, we searched for highly penetrant de novo variants (DNVs) in 50 nsCL/P patient/parent-trios with a low polygenic risk for the phenotype (discovery). We prioritized DNV-carrying candidate genes from the discovery for resequencing in independent cohorts of 1010 nsCL/P patients of diverse ethnicities and 1574 population-matched controls (replication). Segregation analyses and rare variant association in the repli

SUBMITTER: Ishorst N 

PROVIDER: S-EPMC10009911 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature