Epidemiological methods for studying genes and environmental factors in complex diseases

Lancet. 2001 Oct 20;358(9290):1356-60. doi: 10.1016/S0140-6736(01)06418-2.


Exploration of the human genome presents new challenges and opportunities for epidemiological research. Although the case-control design is quicker and cheaper for study of associations between genotype and risk of disease than the cohort design, cohort studies have been recommended because they can be used to study gene-environment interactions. Although the scientific relevance of statistical interaction is pertinent, the main disadvantage of the case-control design-susceptibility to bias when estimating effects of exposures that are measured retrospectively-does not necessarily apply when studying statistical interaction between genotype and environmental exposure. Because correctly designed genetic association studies are equivalent to randomised comparisons between genotypes, conclusions about cause can be drawn from genetic associations even when the risk ratio is modest. For adequate statistical power to detect such modest risk ratios, the case-control design is more feasible than the cohort design.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Case-Control Studies
  • Environmental Exposure*
  • Epidemiology*
  • Female
  • Genetics, Medical*
  • Genotype
  • Humans
  • Research Design*
  • Risk Factors
  • Venous Thrombosis / etiology