A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia

Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown1. Cardiomyopathies due to sarcomeric mutations are a major monogenic cause for heart failure (MIM600958). Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (initial study OR = 5.3 (95% CI = 2.3–13), P = 2 10-6; replication study OR = 8.59 (3.19–25.05), P = 3 10-8; combined OR = 6.99 (3.68–13.57), P = 4 10-11) and that disrupts cardiomyocyte structure in vitro. Its prevalence was found to be high (4%) in populations of Indian subcontinental ancestry. The finding of a common risk factor implicated in South Asian subjects with cardiomyopathy will help in identifying and counseling individuals predisposed to cardiac diseases in this region.