With dTDT and case-control analysis applied to the LinkageMS and CIDRSNP data respectively, we compute the p-values of MH test based on calculations in Table 7 . Figure 6 shows the Manhattan plots of –log10P across all 23 chromosomes from the MH test. The most significant SNP (rs11583322) on chromosome 1 gives a p-value = 1.10×10− 8 that meets the GWAS significance level. This SNP lies in the gene Serine/Threonine Kinase 40 (STK40) that connects pluripotency factor Oct4 to the Erk/MAPK pathway controls extraembryonic endoderm differentiation [80]. Table 8 lists the top SNPs with MH test p-values <10− 5 and their corresponding case-control study and dTDT p-values. From the table we can see that the p-value of each SNP in the MH test is approximately the product of p-values in the other two tests. However, SNPs with high rankings by p-values in the MH test do not systematically correspond to high rankings in the individual tests. The p-values in the dTDT share the highest variance (2.01×10− 3) among the three tests because of the randomness introduced by the inference procedure
