Use of weighted p-values in regional inference procedures

Our previous studies have demonstrated that the power to detect linkage was improved by calculating a moving average of consecutive p-values in a smal l region as compared with testing all single p-valucs. The goal of this stu dy was to test whether the power can be improved further with an alternativ e method whereby the middle p-values in the sequence were given more weight than the others. We also wanted to compare the moving average tests with m ultipoint linkage tests. The simulated extended pedigree data from the gene ral population was analyzed to identify two major genes (MG1 and MG5) under lying two quantitative traits (Q1 and Q5). We used the variance components method implemented in the GENEHUNTER program to test for linkage of 14-mark er regions each on chromosome 19 and chromosome 1 to the adjusted quantitat ive traits Q1 and Q5, respectively, in all 50 replicates. As before, we fou nd that the moving average test was more powerful than a test based on sing le p-values. In some cases, the weighting procedure increased the power fur ther and was similar to that of multipoint analysis, but this was not consi stently found. In addition, all methods had low power and it is not possibl e to make a general conclusion that some weighting schemes are better than others. ((C)) 2001 Wiley-Liss, Inc.