title: Methods for assessing familial aggregation: family history measures and confounding in the standard cohort, reconstructed cohort and case-control designs.
abstract: OBJECTIVE
  To test whether case-control-based familial aggregation studies produce estimates of risk to relatives that are inherently biased or confounded by age and family size, and to compare case-control-derived estimates with those from the reconstructed cohort method. In addition, we test if the definition of family history affects the accuracy of results obtained from either design. We use simulated data, which allows us to know the true data origin.
  
  
  METHODS
  We simulated populations of three generation families. Both a dominant genetic disease and a non-genetic disease were present in the population. We compared the effect estimates from different measures of family history with those derived from the actual genetic cause of disease.
  
  
  RESULTS
  Effect estimates from family history measures that used multiple family members were more accurate than those derived from measures based on a single relative. Neither family size nor age of family members defining family history were confounders in the case-control design.
  
  
  CONCLUSIONS
  The case-control and reconstructed cohort designs are equally valid in assessing familial aggregation of disease.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, New York, NY, USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Zimmerman
authors.forename: Deb K
authors.initials: DK
authors.lastname: Pal
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tin
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D015982:Bias; D016022:Case-Control Studies; D015331:Cohort Studies; D003198:Computer Simulation; D004812:Epidemiologic Methods; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015995:Prevalence; D012680:Sensitivity and Specificity