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Commentary: the affected sib-pair method in the context of an epidemiologic study design
M J Khoury1, W D Flanders, R B Lipton
1Birth Defects and Genetic Diseases Branch, Center for Environmental Health and Injury Control, Centers for Disease Control, Atlanta, Georgia 30333.
Genetic Epidemiology
|January 1, 1991
Summary
The sib-pair methodology offers a framework for family-based epidemiologic studies. This approach analyzes disease risk by comparing genetic similarity among relatives, aiding in the study of gene-environment interactions.
Area of Science:
- Epidemiology
- Genetic Epidemiology
- Family Studies
Background:
- The sib-pair methodology is a well-established tool in genetic research.
- Its application within broader epidemiologic study designs requires a structured framework.
- Family studies, such as those on insulin-dependent diabetes mellitus, provide valuable data for such investigations.
Purpose of the Study:
- To present a framework for integrating the sib-pair methodology into epidemiologic study designs.
- To illustrate the utility of the sib-pair method in family-based epidemiological research using concrete examples.
- To demonstrate how this method can elucidate the roles of genetic loci and environmental factors in disease etiology.
Main Methods:
- Cohort Study Design: Unaffected relatives are followed; disease risk is stratified by the number of alleles identical by descent (ibd) with the proband (0, 1, or 2).
- Case-Control Study Design: Affected relatives (cases) are compared to unaffected relatives (controls) based on the number of alleles ibd with the proband.
- Analysis: Relative risk and odds ratios are computed, with adjustments for covariates (other genetic markers, environmental exposures) using stratified and multivariate analyses.
Main Results:
- In the absence of linkage, disease risks are expected to be similar across different groups of allele sharing (0, 1, 2 ibd).
- The sib-pair approach allows for the computation of relative risk and odds ratios, providing quantitative measures of association.
- Stratified and multivariate analyses enable the evaluation of covariates and gene-environment interactions in relation to disease risk.
Conclusions:
- The sib-pair methodology is adaptable for use in both cohort and case-control family-based epidemiologic studies.
- This approach facilitates the simultaneous investigation of environmental factors and specific gene loci in disease etiology within a single study design.
- Family-based studies employing the sib-pair method are powerful tools for understanding complex disease development.