Genetic epidemiology: some special contributions of birth cohorts

Summary Birth cohorts that collect detailed phenotypic and environmental information, particularly if multigenerational, have an important contribution to make as we seek to understand the genetic and environmental determinants of common disease. Provided such multigenerational population cohorts are unselected by disease, trait or exposure, they can also contribute important information that is needed for optimal statistical analysis in genetic epidemiology generally. One example of this added value is an assessment, at specified loci, of whether or not there is distortion of the expected Mendelian 50 : 50 transmission of alleles to study subjects (e.g. due to differential loss of embryos of one genotype). Another example is to test for heterosis, i.e. whether heterozygotes have a greater or lesser effect than either homozygote. Finally, phenome scans (a fixed format analysis of the associations between a genotype of interest and thousands of outcome variables from the cohort database) could be used as a screening tool to test whether certain classes of genetic variation have more impact than others on human health and development, and so inform genotyping strategies generally.