title: Causal models for investigating complex disease: I. A primer.
abstract: OBJECTIVE
  To illustrate the utility of causal models for research in genetic epidemiology and statistical genetics. Causal models are increasingly applied in risk factor epidemiology, economics, and health policy, but seldom used in statistical genetics or genetic epidemiology. Unlike the statistical models usually used in genetic epidemiology, causal models are explicitly formulated in terms of cause and effect relationships occurring at the individual level.
  
  
  METHODS
  We describe two causal models, the sufficient component cause model and the potential outcomes model, and show how key concepts in genetic epidemiology, including penetrance, phenocopies, genetic heterogeneity, etiologic heterogeneity, gene-gene interaction, and gene-environment interaction, can be framed in terms of these causal models. We also illustrate how potential outcomes models can provide insight into the potential for confounding and bias in the measurement of causal effects in genetic studies.
  
  
  RESULTS
  Our analysis illustrates how causal models can elucidate the relationships among underlying causal mechanisms and measures obtained from statistical analysis of observed data.
  
  
  CONCLUSIONS
  Causal models can enhance research aimed at identifying causal genes.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Madsen
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hodge
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
mesh_terms: D003627:Data Interpretation, Statistical; D056726:Genetic Association Studies / Q000379:methods*; D030342:Genetic Diseases, Inborn / Q000453:epidemiology / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D008954:Models, Biological; D017720:Molecular Epidemiology / Q000379:methods*