Heritability of Mitral Regurgitation: Observations From the Framingham Heart Study and Swedish Population
Francesca N Delling1, Xinjun Li2, Shuo Li2
1From the Boston University's and National Heart, Lung and Blood Institute's Framingham Heart Study, MA (F.N.D., B.T.L., E.W.O., P.S., E.J.B., R.S.V.); Cardiovascular Division, Department of Medicine, University of California San Francisco (F.N.D.); Center for Primary Health Care Research, Lund University, Malmö, Sweden (X.L., B.Z., K.S.); Department of Biostatistics (S.L., Q.Y., V.X.), Department of Epidemiology (V.X., E.J.B., R.S.V.), and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Boston University School of Medicine, MA; Department of Cardiology, Clinical Sciences, Lund University, Sweden (A.M., P.A., J.G.S.); and Skåne University Hospital, Lund, Sweden (A.M., P.A., J.G.S.). Francesca.Delling@ucsf.edu.
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<0.05). In Sweden, sibling MR was associated with a hazard ratio of 3.57 (95% CI, 2.21-5.76; P<0.001) for development of MR.
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.
Insights
Mitral regurgitation (MR) shows familial clustering, indicating a genetic susceptibility that affects various subtypes. This suggests a shared genetic basis for MR, warranting further investigation into common regulatory pathways.
Area of Science:
- Cardiovascular Genetics
- Epidemiology
- Medical Genetics
Background:
- Familial aggregation of primary mitral regurgitation (MR) due to mitral valve prolapse is known.
- This study investigates the heritability of MR across different subtypes, including nonprimary MR.
Purpose of the Study:
- To determine if mitral regurgitation (MR) exhibits familial clustering across various subtypes.
- To estimate the heritability of MR in a large cohort.
Main Methods:
- Analysis of Framingham Heart Study (FHS) Generation 2 and 3 participants and Swedish siblings.
- MR diagnosis via color Doppler (FHS) and International Classification of Diseases codes (Sweden).
- Heritability estimation using pedigree data from 539 FHS pedigrees (7580 individuals).
Main Results:
- MR was more prevalent in individuals with affected siblings (28%) compared to those without (17%) in the FHS cohort (OR, 1.20; P=0.04).
- Heritability estimates for MR in FHS pedigrees ranged from 0.12 to 0.44 (P<0.05), depending on the definition of MR.
- In Sweden, sibling MR significantly increased the hazard for developing MR (HR, 3.57; P<0.001).
Conclusions:
- Familial clustering of mitral regurgitation (MR) is present in the general population.
- This supports a common genetic susceptibility for both primary and nonprimary MR.
- Further research is needed to identify shared genetic pathways underlying MR.
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