Population-based family studies in genetic epidemiology

Lancet. 2005 Oct;366(9494):1397-406. doi: 10.1016/S0140-6736(05)67570-8.


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.

Publication types

  • Review

MeSH terms

  • Case-Control Studies
  • Diseases in Twins / genetics
  • Family*
  • Genetic Predisposition to Disease / genetics*
  • Genetics, Population*
  • Humans
  • Penetrance
  • Research Design