Familial risk of dilated and hypertrophic cardiomyopathy: a national family study in Sweden

Abstract

AimsThis study aims to determine the familial incidence of dilated (DCM) and hypertrophic cardiomyopathy (HCM) in firstdegree, second-degree, and third-degree relatives of affected individuals. Methods and resultsIn this population-based multigenerational cohort study, full-siblings, half-siblings, and cousin pairs born to Swedish parents between 1932 and 2015 were included, and register-based DCM and HCM diagnoses among relatives were ascertained. Adjusted odds ratios (ORs) for DCM and HCM were calculated for relatives of individuals with DCM and HCM compared with relatives of individuals without DCM and HCM for reference. Total study population included 6 334 979 subjects and consisted of 5 577 449 full-siblings, 1 321 414 half-siblings, and 3 952 137 cousins. Overall, 10 272 (0.16%) unique individuals were diagnosed with DCM and 3769 (0.06%) with HCM. Of these, 7716 (75.12%) and 2375 (63.01%) were males, respectively. Familial risk ORs for DCM were 5.35 [95% confidence intervals (CI): 4.85-5.90] for full-siblings, 2.68 (95% CI:1.86-3.87) for half-siblings, and 1.72 (95% CI:1.12-2.64) for cousins of affected individuals. The ORs for HCM were 42.44 (95% CI:37.66-47.82) for full-siblings, 32.70 (95% CI:21.32-50.15) for half-siblings, and 36.96 (95% CI:29.50-46.31) for cousins of affected individuals. In sex-stratified analysis, relatives of affected females were found more likely to be affected than were relatives of affected males, with stronger aggregation observed for HCM. Conclusions Familial risk of HCM and DCM is high and associated with genetic resemblance, with strongest aggregations observed in relatives of affected females with HCM, whereas this association was distinctly attenuated for DCM. The finding of a Carter effect, more pronounced in HCM, suggests a multifactorial threshold model of inheritance.

RNF213 Variants, Vasospastic Angina, and Risk of Fatal Myocardial Infarction

“…A previous GWAS for coronary artery diseases (CADs) or angina pectoris included VSA; however, no stratified analyses have been performed specifically for VSA, to our knowledge. A recent Swedish nationwide study reported high familial heritability for VSA, highlighting the importance of investigating genetic susceptibility. This study aimed to identify genetic factors associated with VSA, and uncover the specific underlying pathologies of VSA.…”

Gender-specific genetic and epigenetic signatures in cardiovascular disease

“…Furthermore, it is noteworthy that while the onset of disease occurs later in women, they face an elevated risk of developing heart failure or death ( 105 ). These observations also suggest that women may require a higher number of genetic alterations to develop heart failure, implying an increased likelihood of transmitting the disease to their offspring ( 106 ).…”

Sex Differences in Heart Failure: What Do We Know?

“…Genetic testing shows that a higher percentage of women carry sarcomere gene variants, with variable effects on disease presentation and progression based on the specific gene variant. In a nationwide family risk study, researchers observed that the relatives of female patients with HCM are more likely to be affected by the disease compared to the relatives of affected males [78]. This finding suggests the possibility of a multifactorial threshold model of inheritance, in which female individuals carry a higher genetic load for HCM.…”

“…Consequently, females would be more likely to transmit the disease to their offspring and have siblings with the disease. This phenomenon is referred to as the Carter effect [78]. This suggests that the genetic factors contributing to HCM susceptibility may differ between males and females, with females requiring a higher genetic burden to manifest the disease.…”