Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis.

ABSTRACT:

Background and aims

It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms.

Approach and results

Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant ( SERPINA1 ; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs;

SUBMITTER: Stonebraker JR 

PROVIDER: S-EPMC11427593 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature