Identification of excess clustering of coronary heart diseases among extended pedigrees in a genealogical population database

Background First-degree family history of early coronary artery disease (CAD) and myocardial infarction (MI) is prognostic among disease-free individuals but may be unreliable. This study evaluated deaths caused by CAD, MI, hypertensive heart disease (HtnHD), and congestive heart failure (CHF) among close and distant relatives. Methods The Utah Population Database contains >2.2 million individual records with genealogy data and 250,000 linked death certificates. Deaths caused by CAD (n = 28,469), MI (n = 26,468), HtnHD (n = 3933), and CHF (n = 11,784) were studied. Familial relative risks (FRRs) were assessed for first- and second-degree relatives. Familiality was also evaluated using the Genealogical Index of Familiality (GIF), which considers close and distant genetic relationships in the Utah Population Database. Results Familial relative risks in first-degree (FRR = 1.25, P < .0001) and second-degree (FRR = 1.06, P = .0002) relatives were significant for early age at MI death (<65 years old). Genealogical Index of Familiality analysis demonstrated excess relatedness for deaths caused by MI (case GIF 2.93, mean control GIF 2.73, P < .001) and CHF (2.92 vs 2.66, P < .001). For early age at death, GIFs were significant for MI (3.06 vs 2.54, P < .001), HtnHD (3.22 vs 2.44, P = .003), and CHF (2.64 vs 2.23, P = .003). Conclusions Deaths caused by MI and CHF demonstrate a heritable component in close and distant relatives. For MI, CHF, and HtnHD, for which findings were more pronounced in early age at death, gene discovery may be most effective among early-onset clusters. Excess relatedness was not found for CAD death—perhaps because of heterogeneity within the phenotype—suggesting that this may be a suboptimal phenotype for genetic study.