The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes.

ABSTRACT: Alpha-1 antitrypsin deficiency (AATD), mainly due to the PI*ZZ genotype in SERPINA1, is one of the most common inherited diseases. Since it is associated with a high disease burden and partially prevented by smoking cessation, identification of PI*ZZ individuals through genotyping could improve health outcomes.We examined the frequency of the PI*ZZ genotype in individuals with and without diagnosed AATD from UK Biobank, and assessed the associations of the genotypes with clinical outcomes and mortality. A phenome-wide association study (PheWAS) was conducted to reveal disease associations with genotypes. A polygenic risk score (PRS) for forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) ratio was used to evaluate variable penetrance of PI*ZZ.Among 458 164

SUBMITTER: Nakanishi T 

PROVIDER: S-EPMC7726845 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature