Using risk-based sampling to enrich cohorts for endpoints, genes, and exposures.
Targeting the first-degree relatives of people with a particular complex disease can offer a powerful approach to building a risk-based cohort for prospective studies of etiologic factors. Such a cohort provides both a sizable increase in the rate of accrual of newly incident cases, enriching for risk factors that are known or even unknown, and a high level of motivation among participants. A nationwide study of breast cancer in the United States and Puerto Rico, the Sister Study, made up of women who are each the sister of a woman with breast cancer, exemplifies this approach. In this paper, the authors provide power calculations to aid in the design of such studies and quantify their benefits for detecting both genetic variants related to risk and interactive effects of genetic and environmental factors. While the risk-based cohort can have markedly increased prevalences of rare causative alleles, most of the power advantages for this design is due to the increased rate of accrual of newly incident cases rather than the increase in any one individual allele.
Weinberg
Clarice R
CR
Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. weinberg@niehs.nih.gov
Shore
David L
DL
Umbach
David M
DM
Sandler
Dale P
DP
D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D015331:Cohort Studies; D004198:Disease Susceptibility; D023381:Endpoint Determination; D004781:Environmental Exposure / Q000009:adverse effects*; D015340:Epidemiologic Research Design; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015995:Prevalence; D011446:Prospective Studies; D012306:Risk; D035781:Siblings