Case-control and case-only designs with genotype and family history data: estimating relative risk, residual familial aggregation, and cumulative risk.
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.
Chatterjee
Nilanjan
N
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6210 Executive Boulevard, Rockville, Maryland 20852, USA. chattern@mail.nih.gov
Kalaylioglu
Zeynep
Z
Shih
Joanna H
JH
Gail
Mitchell H
MH
D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D016022:Case-Control Studies; D005192:Family Health; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008487:Medical History Taking; D015233:Models, Statistical; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis; D016016:Proportional Hazards Models; D012306:Risk
D019313:BRCA1 Protein; D024682:BRCA2 Protein