Large Life-Course Cohorts for Characterizing Genetic and Environmental Contributions

Abstract

arge studies of thousands of ordinary infants, followed closely from to adulthood and even into late life, provide a unique resource for illuminating the underlying causes of the health problems of early (and later) life.1 The mother's state of health just before conception, now thought to be potentially important to her offspring's lifelong health, should also be included when feasible. This type of study, usually termed a birth is critical to understanding the complex way that various health conditions unfold at various ages, depending on both genetic characteristics and the precise nature and sequence of environmental exposures that each child has experienced since conception. In a single cohort, it is efficient to measure a large number of potential risk and protective factors and analyze them against the occurrence of a large number of common health outcomes (diseases and dysfunctions). The only essential requirement is that the right physical and social exposures in early life are selected and that suitable multiple measurements are made as the child ages. For example, appropriate samples of blood, urine, and so on, can provide a physiological record of environmental exposures (such as absorbed environmental contaminants at a given age) or early/intermediary health effects (such as altered daily cycles of stress hormones in the saliva or blood). Because a single large cohort offers an efficient long-term research investment for studying a wide variety of risk and protective factors, and subsequent health and develop mental trajectories, we label such cohorts as research platforms. Such a platform can ultimately support literally hundreds of specific spinoff studies over succeeding decades. Furthermore, only core data collection and storage costs need to be funded directly within the essential cohort infrastructure. Specific studies to make use of these stored questionnaire and physical examination data and biologic samples can be initiated as new scientific concepts and societal needs emerge. Cohort studies can start later in life as well. The gigantic U.K. BioBank platform will collect baseline interview data and blood samples for genetic and other analyses from some 500,000 healthy Britons over age 45. This study is intended to elucidate the joint genetic and environmental determinants of common conditions of later life-hypertension, diabetes, heart disease, and some cancers-as they develop and are reported through the U.K. National Health Service. Such a late-life study will, of course, have limited ability to uncover new early-life causes of these late-life diseases unless those early-life factors can be reliably remembered by the study subjects after 50 years or more or were recorded at the time in a way that is currently accessible.2 Several countries, recognizing the power of the cohort approach, are either in the early stages of initiating such cohorts or have plans to do so. Typically, these cohorts