THBS2 Is a Candidate Modifier of Liver Disease Severity in Alagille Syndrome.

ABSTRACT:

Background & aims

Alagille syndrome is an autosomal-dominant, multisystem disorder caused primarily by mutations in JAG1, resulting in bile duct paucity, cholestasis, cardiac disease, and other features. Liver disease severity in Alagille syndrome is highly variable, however, factors influencing the hepatic phenotype are unknown. We hypothesized that genetic modifiers may contribute to the variable expressivity of this disorder.

Methods

We performed a genome-wide association study in a cohort of Caucasian subjects with known pathogenic JAG1 mutations, comparing patients with mild vs severe liver disease, followed by functional characterization of a candidate locus.

Results

We identified a locus that reached suggestive genome-level significance upstream o

SUBMITTER: Tsai EA 

PROVIDER: S-EPMC5042888 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature