THE WEIGHTED RANK PAIRWISE CORRELATION STATISTIC FOR LINKAGE ANALYSIS- SIMULATION STUDY AND APPLICATION TO ALZHEIMERS-DISEASE

The weighted rank pairwise correlation (WRPC) statistic has been propo sed as a robust test of genetic linkage, particularly adapted to the a nalysis of large and complex pedigrees and for age-dependent and heter ogeneous diseases. In this paper a simulation study is presented. Vali dity and power of the WRPC test are studied and compared to the Hasema n-Elston sibpair method for various types of problems. The power of th e WRPC test is slightly lower than the Haseman-Elston method for analy zing a large number of small randomly chosen pedigrees. It is higher h owever in presence of genetic heterogeneity or for analyzing large ind ividual pedigrees. Recently, evidence of linkage of Alzheimer's diseas e 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 Led-score method. The WRPC test statist ic is higher than the equivalent Lod-score statistic for the two pedig rees which show strong evidence of linkage with the two methods. The g lobal WRPC test statistic is slightly lower than the Lod-score test st atistic. The WRPC test, however, makes no hypothesis of a specific gen etic transmission model and can be computed very quickly; in addition, an exact P-value can be computed by simulation for individual pedigre es. (C) 1994 Wiley-Liss, Inc.