Inheritance Impacts Mitral Valve Insufficiency.

Abstract

As the field of cardiovascular genetics continues to evolve, traditional Mendelian disorders are more readily characterized by clinical genetic testing. These conditions are caused by rare DNA mutations with major effects for most, if not all carriers. The newest frontiers for genetic investigation include more common disorders in which the genetic variants are more prevalent and the effect sizes are smaller. The spectrum extends from severe neonatal disorders with high penetrance to more common diseases, such as familial mitral valve prolapse (MVP). Pushing this envelope, investigators in this issue of Circulation: Cardiovascular Genetics now report heritability of mitral regurgitation (MR).1 Starting with the well-characterized Framingham Heart Study participants in whom second- and third-generation cardiac data were available, they identified 1062 with ≥mild MR among 5132 (21%), in whom there was adequate parental and sibling information. The odds ratio of MR was 1.42 if parental MR was present after adjusting for age, sex, and risk factors and with restricting to ≥moderate MR. Likewise, the odds ratio of MR was 1.78 if sibling MR was present after adjusting for age, sex, and risk factors and restricting to ≥moderate MR. Strengthening their conclusions, the authors used the Swedish hospital registry to validate these findings. In Sweden, 1.2% (239 of 18 891) of siblings with sibling MR had MR compared with 0.2% (n=8389/5 138 298) without sibling MR, corresponding to a hazard ratio of 4.0 adjusted for age and sex. MR is more commonly seen in the context …