A burden of rare variants in BMPR2 and KCNK3 contributes to a risk of familial pulmonary arterial hypertension.

ABSTRACT:

Background

Pulmonary arterial hypertension (PAH) is a severe lung disease with only few effective treatments available. Familial cases of PAH are usually recognized as an autosomal dominant disease, but incomplete penetrance of the disease makes it difficult to identify pathogenic variants in accordance with a Mendelian pattern of inheritance.

Methods

To elucidate the complex genetic basis of PAH, we obtained whole exome- or genome-sequencing data of 17 subjects from 9 families with heritable PAH and applied gene-based association analysis with 9 index patients and 300 PAH-free controls.

Results

A burden of rare variants in BMPR2 significantly contributed to the risk of the disease (p = 6.0 × 10^-8). Eight of nine families carried four previously reported si

SUBMITTER: Higasa K 

PROVIDER: S-EPMC5383973 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature