Background The clinical significance of variants in genes associated with inherited cardiomyopathies can be difficult to determine due to uncertainty regarding population genetic variation and a surprising amount of tolerance of the genome even to loss of function variants. We hypothesized that genes associated with cardiomyopathy might be particularly resistant to the accumulation of genetic variation. Methods and Results We analyzed the rates of single nucleotide genetic variation in all known genes from the exomes of >5,000 individuals from the National Heart, Lung, and Blood Institute’s Exome Sequencing Project (ESP), as well as the rates of structural variation from the Database of Genomic Variants. Most variants were rare, with over half unique to one individual. Cardiomyopathy associated genes exhibited a rate of nonsense variants 96.1% lower than other Mendelian disease genes. We tested the ability of in-silico algorithms to distinguish between a set of variants in MYBPC3, MYH7, and TNNT2 with strong evidence for pathogenicity and variants from the ESP data. Algorithms based on conservation at the nucleotide level (GERP, PhastCons) did not perform as well as amino acid level prediction algorithms (Polyphen-2, SIFT). Variants with strong evidence for disease causality were found in the ESP data at prevalence higher than expected. Conclusions Genes associated with cardiomyopathy carry very low rates of population variation. The existence in population data of variants with strong evidence for pathogenicity suggests that even for Mendelian disease genetics, a probabilistic weighting of multiple variants may be preferred over the ‘single gene’ causality model.

African American participation in Alzheimer’s disease (AD) research studies has been historically low. To determine if older African Americans and Caucasians had different knowledge or attitudes related to AD, we administered the Alzheimer’s Disease Knowledge Scale (ADKS) to 67 older African Americans and 140 older Caucasians in the greater Atlanta area, as well as questions targeting locus of control over general health and AD risks. Older African Americans scored slightly lower on ADKS than older Caucasians, with race only accounting for 1.57 (95% CI 0.57–2.61, p < 0.001) points of difference in a mutli-variate model. Attitudes towards AD were also similar between the two groups, but one in three (35.7%) adults reported control over general health but not AD risks. In addition to enhancing education content in outreach efforts, there is an urgent need to address the perception that future AD risks are beyond one’s own internal control.

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