Heritability of Mitral Regurgitation : Observations From the Framingham Heart Study and Swedish Population
2017
Background— Familial aggregation has been described for primary mitral regurgitation (MR) caused by mitral valve prolapse. We hypothesized that heritability of MR exists across different MR subtypes including nonprimary MR. Methods and Results— Study participants were FHS (Framingham Heart Study) Generation 3 (Gen 3) and Gen 2 cohort participants and all adult Swedish siblings born after 1932 identified in 1997 and followed through 2010. MR was defined as ≥ mild regurgitation on color Doppler in FHS and from International Classification of Diseases codes in Sweden. We estimated the association of sibling MR with MR in Gen 2/Gen 3/Swedish siblings. We also estimated heritability of MR in 539 FHS pedigrees (7580 individuals). Among 5132 FHS Gen 2/Gen 3 participants with sibling information, 1062 had MR. Of siblings with sibling MR, 28% (500/1797) had MR compared with 17% (562/3335) without sibling MR (multivariable-adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.01–1.43; P =0.04). When we combined parental and sibling data in FHS pedigrees, heritability of MR was estimated at 0.15 (95% CI, 0.07–0.23), 0.12 (95% CI, 0.04–0.20) excluding mitral valve prolapse, and 0.44 (95% CI, 0.15–0.73) for ≥ moderate MR only (all P P Conclusions— Familial clustering of MR exists in the community, supporting a genetic susceptibility common to primary and nonprimary MR. Further studies are needed to elucidate the common regulatory pathways that may lead to MR irrespective of its cause.
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