Abstract
The use of family data has a long history in genetics, for association as well as linkage and segregation. Perhaps the simplest and most intuitively obvious example involving association analysis is a study comparing the genotypes in cases with the genotypes in their unaffected siblings. By using an unaffected sibling as a control, we eliminate issues of confounding by population substructure which are caused by comparing affected cases with unaffected controls whose genetic backgrounds are not comparable to the cases. With family controls, rejecting the null hypothesis of no association implies more than just ‘no association’. Finding a significant difference in genotype frequencies between cases and their unaffected siblings implies that the marker is both linked and associated with a disease locus underlying the trait (Appendix C).
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Laird, N.M., Lange, C. (2011). Association Analysis in Family Designs. In: The Fundamentals of Modern Statistical Genetics. Statistics for Biology and Health. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7338-2_9
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