Abstract
Both maternal and paternal disease history can be important predictors of the risk of common conditions such as heart disease or cancer because of shared environmental and genetic risk factors. Sometimes maternal and paternal history can have remarkably different effects on offspring's status. The results are often affected by how the maternal and paternal disease histories are quantified. We proposed using the log-rank score (LRS) to investigate the separate effect of maternal and paternal history on diseases, which takes parental disease status and the age of their disease onset into account. Through simulation studies, we compared the performance of the maternal and paternal LRS with simple binary indicators under two different mechanisms of unbalanced parental effects. We applied the LRS to a national cohort study to further segregate family risks for heart diseases. We demonstrated using the LRS rather than binary indicators can improve the prediction of disease risks and better discriminate the paternal and maternal histories. In the real study, we found that the risk for stroke is closely related with maternal history but not with paternal history and that maternal and paternal disease history have similar impact on the onset of myocardial infarction.
Highlights
Complex diseases including heart diseases, hypertension, and breast cancer often aggregate within families and disease history of ancestors is often correlated with the disease outcomes of descendants due to common environmental and inherited genetic factors
Maternal history plays a larger role in Alzheimer's disease, type 2 diabetes, and breast cancer compared with paternal history [1,2,3]; only paternal not maternal family history was associated with lumbar spine bone mineral density [4]
We found that only the maternal stroke history but not the paternal history was related to the stroke incidences of offspring and that the influences from parental histories on myocardial infarction (MI) were well balanced
Summary
Complex diseases including heart diseases, hypertension, and breast cancer often aggregate within families and disease history of ancestors is often correlated with the disease outcomes of descendants due to common environmental and inherited genetic factors. Maternal history plays a larger role in Alzheimer's disease, type 2 diabetes, and breast cancer compared with paternal history [1,2,3]; only paternal not maternal family history was associated with lumbar spine bone mineral density [4]. We believe that evaluating the effect of parental disease history on diseases and segregating maternal and paternal history can provide a better understanding of the disease risk factors, improve the accuracy of risk assessment, and allow clinicians to better target on high-risk individuals. In a recent national cohort study, we quantified parental disease history and investigated their associations with heart diseases
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