A robust method for the detection of linkage in familial disease

A nonparametric method for the detection of critical genes associated with familial disease was presented. The method involves the detection of deviations from expected identity by descent distributions at polymorphic marker loci for affected sib pairs. The method thus avoids the difficulties arising from incomplete penetrance, variable age of onset and other complications present in other forms of linkage analysis. The theoretical properties of method were worked out in detail for two important cases -- that of an incompletely penetrant recessive or incompletely penetrant dominant critical autosomal gene linked to a codominant marker locus. An easily implementable decision rule for the detection of linkage was proposed, and its operating characteristics for a variety of alternative hypothesis were obtained.