Case-control and case-only designs with genotype and family history data: estimating relative risk, residual familial aggregation, and cumulative risk

Biometrics. 2006 Mar;62(1):36-48. doi: 10.1111/j.1541-0420.2005.00442.x.

Abstract

In case-control studies of inherited diseases, participating subjects (probands) are often interviewed to collect detailed data about disease history and age-at-onset information in their family members. Genotype data are typically collected from the probands, but not from their relatives. In this article, we introduce an approach that combines case-control analysis of data on the probands with kin-cohort analysis of disease history data on relatives. Assuming a marginally specified multivariate survival model for joint risk of disease among family members, we describe methods for estimating relative risk, cumulative risk, and residual familial aggregation. We also describe a variation of the methodology that can be used for kin-cohort analysis of the family history data from a sample of genotyped cases only. We perform simulation studies to assess performance of the proposed methodologies with correct and mis-specified models for familial aggregation. We illustrate the proposed methodologies by estimating the risk of breast cancer from BRCA1/2 mutations using data from the Washington Ashkenazi Study.

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Case-Control Studies*
  • Family Health*
  • Genotype
  • Humans
  • Likelihood Functions
  • Medical History Taking
  • Models, Statistical*
  • Mutation
  • Neoplasms / diagnosis
  • Proportional Hazards Models
  • Risk*

Substances

  • BRCA1 Protein
  • BRCA2 Protein