Commentary: the affected sib-pair method in the context of an epidemiologic study design.
The purpose of this commentary is to provide a framework for using the well-known sib-pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin-dependent diabetes mellitus, we illustrate that the sib-pair method can be used in family-based epidemiologic studies. In a cohort study, unaffected relatives of probands ascertained from well-defined populations are followed for disease development. Disease risks are then stratified according to the number of alleles at one or more loci (0, 1, 2) that are identical by descent (ibd) with the proband. In the absence of linkage between the marker locus and the disease locus, disease risks are expected to be identical in the three groups. Measures of relative risk can be computed (with share-0 as baseline group). In a case-control study, relatives of probands that become affected (cases) are compared to a sample of relatives of probands that stay unaffected (controls) with respect to the number of alleles ibd with the proband. Measures of odds ratio can be computed (with share-0 as baseline group). In both cohort and case-control approaches, covariates including other genetic markers and environmental exposures can be evaluated in relation to disease risk and also for evidence of interaction with the specific marker of interest using stratified and multivariate analyses. Family-based epidemiologic studies allow investigators to study, in a single design, the role of environmental factors and specific gene loci in the etiology of diseases.
Khoury
M J
MJ
Birth Defects and Genetic Diseases Branch, Center for Environmental Health and Injury Control, Centers for Disease Control, Atlanta, Georgia 30333.
Flanders
W D
WD
Lipton
R B
RB
Dorman
J S
JS
D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004812:Epidemiologic Methods; D005190:Family; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D012107:Research Design; D012307:Risk Factors; D015983:Selection Bias
D006680:HLA Antigens