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...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...replication study OR = 8.59...combined OR = 6.99....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.
The odds ratio is showing a large effect for this deletion; the likelihood of heart related problems if you carry the deletion are very high. On the order of 90% of older individuals who carry it have heart problems. On the other hand, only around 5% of the heart disease among South Asians is due to this locus of large effect. Why is this genetic variant so common? The authors suggests that since it has an effect only later in life, beyond reproductive age, selection has not been able to purge the allele. On the other hand, a 5% frequency is rather high, perhaps it is just a neutral variant which become common due to some population bottleneck in South Asia within the last 30,000 years. Or, perhaps antagonstic pleiotropy, by which I mean benefits early in life (which would increase reproductive fitness greatly) outweighing the relatively limited fitness effects later on in life (older individuals can increase the fitness of their offspring through investment in resources, but this is less important or likely than direct increase in fitness during peak reproductive years). In some ways this deletion in MYBPC3 is the South Asian cystic fibrosis, at least in terms of frequency. But CF hits people early on it life and so its evolutionary impact is much stronger. Here's a figure which shows the effect in those with the allele:
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