Because population stratification was not simulated in GAW15, we did not adjust the genotype data using principal component procedures. We directly applied the test to the 9187 SNPs, and identified four SNPs whose p
-values are far less than the Bonferroni corrected p
-value 0.05/9187 = 5.44 × 10-6
. We used the software Haploview [4
] to test the linkage disequilibrium pattern among them. The D
' scores among SNP6-152, SNP6-153, and SNP6-154 are above 0.93, suggesting strong LD, and the D
' between SNP6-155 and the rest was less than 0.38. Next, we applied a case-control chi-square test to the unrelated 200 cases and controls, and a family-based test (transmission-disequilibrium test, or TDT) to the family data. As a comparison, we also applied our test zfam
only to the family data. All the test results were consistent, and are summarized in Table . The squares of the new test value z
are strictly larger than the square sum of the corresponding chi-square test and TDT. For the family data, the value of our statistic zfam
is also bigger than the value of TDT test statistic. These suggest that the proposed combined test has improved power. Also, as expected, the values of test statistic z
are much larger than the test statistic zfam
, which is restricted only to families, because more information from the unrelated case-control sample is used.
The most significant SNPs out of the total 9187 markers and their test values with associated p-values before Bonferroni correction.
The type I errors of the proposed test are reasonable and comparable to the other two tests, which are listed in Table . At the significance level α = 0.05, we observed 483 SNPs with p-values less than 0.05, giving a slightly higher type I error rate of 0.0525, which might be caused by correlation with disease loci. Thus, we excluded all the 674 SNPs on chromosome 6, and then observed 433 SNPs with p-value less than 0.05, with a corresponding type I error of 0.0508 (Table ). Next, we applied our test to the dense map of chromosome 6, and got 56 significant SNPs whose p-values are less than the Bonferroni corrected p-value 0.05/(17820 + 9187) = 1.85 × 10-6. In particular, the markers 3439, 3442, 3437, 3436, 3440, 3430, and 3426 have the largest test value. Together with the LD patterns from Haploview, we conclude that the most likely interval for a major gene is between 49.4262 cM and 49.5184 cM on chromosome 6.
Type I error rates of different tests for all markers except those on chromosome 6.