Evidence for a heritable component in death resulting from aortic and mitral valve diseases.
BACKGROUND
Cardiac valvular diseases contribute to >42,000 deaths yearly in the United States, but the role of genetics in these deaths is unknown. This study evaluated the familiality of death resulting from aortic, mitral, and all valvular diseases using a population-based genealogy linked to death records.


RESULTS
The Utah Population Database contains >2 million individual records with genealogy data and 250,000 linked death certificates. Nonrheumatic aortic (n=932), mitral (n=1165), and all valvular (n=2504) disease deaths and rheumatic heart disease deaths (n=4713) were studied. Familial relative risks (FRRs) were assessed for first- and second-degree relatives. Familiality was also evaluated with the genealogical index of familiality, which considers all relationships in the Utah Population Database. FRRs were increased only for mitral valve death in both first-degree (FRR, 2.55; P<0.0001) and second-degree (FRR, 1.67; P<0.0001) relatives. Genealogical index of familiality analysis showed significant excess relatedness for all groups (P<0.001). Genealogical index of familiality results (P<0.001) for early age at death cases showed higher mean relatedness, a common characteristic of heritable disorders. Excess familiality extended to distant relatives for mitral (second-degree relatives) and aortic (beyond second-degree relatives) valve death.


CONCLUSIONS
Deaths resulting from nonrheumatic mitral and aortic diseases clustered among both close and distant relatives, especially among early age at death cases, suggesting a significant genetic component in death resulting from valvular diseases. Future studies should focus on gene discovery.
Horne
Benjamin D
BD
Genetic Epidemiology Division, Department of Medical Informatics, University of Utah, 391 Chipeta Way, Suite D, Salt Lake City, UT 84108-1266, USA. benjamin@genepi.med.utah.edu
Camp
Nicola J
NJ
Muhlestein
Joseph B
JB
Cannon-Albright
Lisa A
LA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve; D002423:Cause of Death; D003644:Death Certificates; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006349:Heart Valve Diseases / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D038801:International Classification of Diseases; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve; D010641:Phenotype; D012214:Rheumatic Heart Disease / Q000235:genetics / Q000401:mortality; D012306:Risk; D014589:Utah / Q000453:epidemiology