Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies.

摘要: Purpose To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate extent to which it may represent a distinct pathology or secondary phenotype associated with other cardiac diseases. Methods We performed rare variant association analysis 840 LVNC cases 125,748 gnomAD population controls, compared results similar analyses on dilated cardiomyopathy (DCM) hypertrophic (HCM). Results observed substantial overlap indicating that often represents phenotypic variation DCM HCM. In contrast, truncating variants in MYH7, ACTN2, PRDM16 were uniquely reflect etiology. particular, MYH7 (MYH7tv), generally considered nonpathogenic for cardiomyopathies, 20-fold enriched over controls. MYH7tv heterozygotes identified UK Biobank healthy volunteer cohorts also displayed significantly greater matched RYR2 exon deletions HCN4 transmembrane LVNC, supporting prior reports arrhythmogenic phenotypes. Conclusion is characterized by DCM/HCM but arrhythmia etiologies. These will enable enhanced application testing help distinguish pathological from physiological noncompaction.