A new statistical test for linkage heterogeneity.

Abstract

A new, statistical test for linkage heterogeneity is described. It is a likelihood-ratio test based on a beta distribution for the prior distribution of the recombination fraction among families (or individuals). The null distribution for this statistic (called the B-test) is derived under a broad range of circumstances. Two other heterogeneity test statistics--the admixture test or A-test first described by Smith and Morton's test (here referred to as the K-test)--are also examined. The probability distribution for the K-test statistic is very sensitive to family size, whereas the other two statistics are not. All three statistics are somewhat sensitive to the magnitude of the recombination fraction theta. Critical values for each of the test statistics are given. A conservative approximation for both the A-test and B-test is given by a chi 2 distribution when P/2 instead of P is used for the observed significance level. In terms of power, the B-test performs best among the three tests over a broad range of alternate heterogeneity hypotheses--except for the specific case of admixture with loose linkage, in which the A-test performs best. Overall, the difference in power among the three tests is not large. An application to some recently published data on the fragile-X syndrome and X-chromosome markers is given.