Nationwide Family Studies of Cardiovascular Diseases – Clinical and Genetic Implications of Family History

Studies of family history (FH) have long been used to estimate the heritability of cardiovascular diseases (CVDs). Genome-wide association studies (GWAS) of several CVDs, such as coronary heart disease (CHD), stroke, aortic aneurysm (AA), atrial fibrillation (AF), and venous thromboembolism (VTE), have found several novel gene loci and have revealed new biological mechanisms. However, most of the heritability for common CVDs remains to be discovered. Studies of FH will continue to be the easiest way to measure the inherited and non-genetic component of a CVD, as FH represents the sum of interactions between environmental and genetic factors. Many past FH studies of CVDs were hampered by recall and selection bias, small study sizes, retrospective case-control study designs, and a lack of follow-up data. Large nationwide register-based follow-up studies of FH have become possible in countries such as Sweden, Denmark, and Iceland. For instance, nationwide family studies of CVDs such as CHD, stroke, AA, AF, and VTE have been published. Such nationwide family studies may be very helpful for the planning of genetic studies to identify the missing heritability of CVDs. Moreover, reliable estimates of the familial risks of CVDs may be helpful for clinical risk assessment. In this article, the design, methodology, results, clinical and genetic implications, and pros and cons of nationwide FH studies are reviewed. The focus is on studies based on Swedish healthcare data. New findings from these studies will be summarised, and future opportunities will be presented.