To type or not to type: The use of unaffected siblings in nonparametric linkage analysis

Unaffected individuals are often disregarded in nonparametric linkage analy sis. Because of the presumed high complexity of genetic interactions and th e resulting low penetrance of any single genetic effect, the statistical co ntribution of unaffected sib pairs is thought to be considerably lower than that of the affecteds. However, in cases where a large number of unaffecte d family members are available for genotyping - as is the case in the simul ated Genetic Analysis Workshop 12 data set - the relatively low value of th e unaffected sibs may be offset by their number. In this paper, I demonstra te that unaffected siblings do contain a significant amount of statistical information, and show that the most powerful method of nonparametric analys is utilizes both affected and unaffected individuals. I also show that sele cting the unaffected individuals based on their age is the most cost effect ive and usually the most powerful strategy. (C) 2001 Wiley-Liss, Inc.