Design Considerations in a Sib-Pair Study of Linkage for Susceptibility Loci in Cancer
Author Information
Author(s): Richard A. Kerber, Christopher I. Amos, Beow Y. Yeap, Dianne M. Finkelstein, Duncan C. Thomas
Primary Institution: Huntsman Cancer Institute, Salt Lake City, UT, USA
Hypothesis
How do design factors impact the efficiency of sib-pair studies in identifying genetic loci associated with colorectal cancer?
Conclusion
Genotyping parents and unaffected siblings is useful for detecting genotyping errors and if allele frequencies are uncertain.
Supporting Evidence
- Power and efficiency were most affected by the number of affected sibs and the number of sib pairs genotyped.
- Genotyping unaffected siblings added little power for low penetrance models but improved validity of tests with genetic heterogeneity.
- The efficiency of the concordant-only test was nearly always better than the concordant-discordant test.
Takeaway
This study looks at how to best design studies that find genes linked to cancer by using siblings. It shows that including parents and siblings who are not affected can help make the results more accurate.
Methodology
Simulation studies were conducted to assess the impact of design factors on the efficiency of linkage studies for colorectal cancer.
Potential Biases
Potential biases due to population heterogeneity and allele frequency misspecification.
Limitations
The study primarily focuses on simulation results, which may not fully capture real-world complexities.
Participant Demographics
The study involves families with a history of colorectal cancer, specifically focusing on affected and unaffected siblings.
Digital Object Identifier (DOI)
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