The weighted rank pairwise correlation statistic for linkage analysis: simulation study and application to Alzheimer's disease.
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.
Commenges
D
D
INSERM U330, Bordeaux, France.
Olson
J
J
Wijsman
E
E
D000544:Alzheimer Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D013223:Statistics as Topic
D005819:Genetic Markers