The weighted rank pairwise correlation statistic for linkage analysis: Simulation study and application to Alzheimer's disease

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Abstract
The weighted rank pairwise correlation (WRPC) statistic has been proposed as a robust test of genetic linkage, particularly adapted to the analysis of large and complex pedigrees and for age‐dependent and heterogeneous diseases. In this paper a simulation study is presented. Validity and power of the WRPC test are studied and compared to the Haseman‐Elston sibpair method for various types of problems. The power of the WRPC test is slightly lower than the Haseman‐Elston method for analyzing a large number of small randomly chosen pedigrees. It is higher however in presence of genetic heterogeneity or for analyzing large individual pedigrees. Recently, evidence of linkage of Alzheimer's disease with a locus on chromosome 14, D14s43, has been obtained by the Lod‐score method. We reanalyze these data using the WRPC test, essentially confirming the results of the Lod‐score method. The WRPC test statistic is higher than the equivalent Lod‐score statistic for the two pedigrees which show strong evidence of linkage with the two methods. The global WRPC test statistic is slightly lower than the Lod‐score test statistic. The WRPC test, however, makes no hypothesis of a specific genetic transmission model and can be computed very quickly; in addition, an exact P‐value can be computed by simulation for individual pedigrees.