title: Population-based family studies in genetic epidemiology.
abstract: Designs that involve families (the traditional strength of genetic epidemiology) and population-based sampling (the traditional strength of environmental epidemiology) allow investigation of both genes and environment, separately or together, and allow valid inference to the population. These case-control-family designs (including those involving twin pairs), can be regarded as retrospective cohort studies of relatives, and can be used for: determining familial risks and genetic models; estimating risk (penetrance) for measured genotypes; genetic association studies; stratifying risks by family history and known mutation status; and studying modifiers of risk in genetically susceptible individuals. Follow-up of families allows genetic and environmental risks to be studied prospectively. We discuss statistical methods, theoretical and practical strengths, limitations, and other issues. Given their versatility, population-based family studies could become a principal framework in epidemiology, and move genetics from its traditional focus on high-risk families to give it a wider clinical and population health relevance.
authors.affiliation: University of Melbourne, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, 723 Swanston Street, Carlton, Victoria 3053, Australia. j.hopper@unimelb.edu.au
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
mesh_terms: D016022:Case-Control Studies; D004200:Diseases in Twins / Q000235:genetics; D005190:Family; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D019683:Penetrance; D012107:Research Design