A new test statistic for linkage applied to bipolar disorder and marker D18S41

We applied a new test statistic for linkage that removes the traditional assumption of equal female (theta f) and male (theta m) recombination fractions by testing Ho: theta f + theta m = 1 vs. HA: theta f + theta m < 1 to GAW10 Problem 1. Specifically we reanalyzed the reported possible linkage between a suggested susceptibility locus for bipolar affective disorder and marker D18S41 on chromosome 18 [Stine et al., 1995]. We used penetrance functions fitting the description of those used by Stine et al. [1995] assuming a continuous age-dependent logistic distribution. Maximum likelihood marker allele frequencies were estimated assuming Hardy-Weinberg equilibrium. Results from the traditional lod-score analyses do not strongly support the existence of linkage between the disease locus and marker D18S41. Similarly, the new test statistic for linkage failed to provide evidence in support of linkage. This was true whether dominant or recessive models of inheritance were assumed, and whether the analyses included all available pedigrees or were confined to paternally transmitted pedigrees. The appreciable difference found between our lod scores and those obtained by Stine et al. [1995] can be attributed to differences in the assumptions made regarding the age-dependent penetrance function, the marker allele frequencies, or both.