A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta.

ABSTRACT:

Aims

Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA.

Methods and results

We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10-22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show t

SUBMITTER: Bjornsson T 

PROVIDER: S-EPMC6127890 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature