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 small region as compared with testing all single p-values. The goal of this study was to test whether the power can be improved further with an alternative 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 multipoint linkage tests. The simulated extended pedigree data from the general population was analyzed to identify two major genes (MG1 and MG5) underlying two quantitative traits (Q1 and Q5). We used the variance components method implemented in the GENEHUNTER program to test for linkage of 14-marker regions each on chromosome 19 and chromosome 1 to the adjusted quantitative traits Q1 and Q5, respectively, in all 50 replicates. As before, we found that the moving average test was more powerful than a test based on single p-values. In some cases, the weighting procedure increased the power further and was similar to that of multipoint analysis, but this was not consistently found. In addition, all methods had low power and it is not possible to make a general conclusion that some weighting schemes are better than others.
Yang
X
X
Genetic Epidemiology Branch, DCEG/NCI/NIH, Bldg. EPS/Rm. 7005, 6120 Executive Blvd., Rockville, MD 20852, USA.
Goldstein
A M
AM
Chase
G A
GA
Gastwirth
J L
JL
Goldin
L R
LR
D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D005828:Genetics, Population; D006801:Humans; D008432:Mathematical Computing; D008957:Models, Genetic; D019655:Quantitative Trait, Heritable; D012984:Software