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Assessing familial aggregation of congenital cardiovascular malformations in case-control studies
N E Maestri1, T H Beaty, K Y Liang
1Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Insights
Familial risk for congenital cardiovascular malformations (CCVM) is higher for relatives of affected individuals. The risk is significantly increased for heart defects involving blood flow, but not for other types.
Area of Science:
- Cardiovascular Genetics
- Pediatric Cardiology
- Epidemiology
Background:
- Congenital cardiovascular malformations (CCVM) represent a significant public health concern.
- Previous studies suggest familial aggregation of CCVM, but the extent varies by defect type.
- Understanding familial risk is crucial for genetic counseling and early intervention.
Purpose of the Study:
- To quantify the familial risk of CCVM based on the type of defect in the index case.
- To investigate the influence of demographic factors on CCVM familial aggregation.
- To differentiate between environmental and genetic contributions to familial risk.
Main Methods:
- Logistic regression analysis was employed to assess CCVM risk in relatives of cases versus controls.
- Data from 3,908 first-degree relatives of 570 matched cases and controls were analyzed.
- The Baltimore-Washington Infant Study provided the dataset for this research.
Main Results:
- Overall risk for any CCVM was four times higher in case relatives compared to control relatives.
- Relatives of cases with flow lesions (e.g., heart defects, VSD) showed a five-fold increased risk.
- No significant increase in risk was observed for relatives of non-flow lesion cases; demographic factors showed no effect.
Conclusions:
- Familial aggregation of CCVM is strongly associated with specific defect types, particularly flow lesions.
- While familial risk is elevated, the specific environmental or genetic sources remain undetermined.
- Further research is needed to elucidate the etiology of CCVM familial aggregation.
Abstract:
Recent data indicate that the familial aggregation of congenital cardiovascular malformations (CCVM) varies with the type of defect in the index case. Using a logistic regression model that allows for dependence among family members, we calculated the risk of any CCVM to case relatives compared with relatives of controls. Data from 3,908 first-degree relatives of 570 matched cases and controls identified from 1981 through 1985 by the Baltimore-Washington Infant Study were used in the analyses. Overall risk for any CCVM in case relatives was increased four-fold over that of control relatives. While relatives of cases with flow lesions (including right and left heart defects, as well as perimembranous ventricular septal defect [VSD]) had a five-fold increase in risk, the risk to relatives of nonflow lesion cases did not differ significantly from the risk to relatives of controls. Sex, maternal age, miscarriage history in the mother, and birth order had no apparent effect on risk among siblings. However, there was an indication of increased risk in relatives of nonwhite cases with VSD compared to relatives of matched controls. However, with these data it was not possible to distinguish between environmental and genetic sources of this familial aggregation.