Table 1.

Observed False-Positive Rates (False-Discovery Rates) for Procedures with Nominal 5% Rates in the Context of Testing Five Possible Gene × Gene Interactions, Calculated from 500 Simulated Data Sets^[Note]

	False-Positive Rate under Model
Procedurea	Null I	Null II
CDF	.194	.214
Simes	.032	.036
RSimes	.048	.058
	False-Discovery Rate under Model
	Null I	Null II
BHD	.014	.014
DRW	.050	.070

Note.— Six SNPs were simulated for 100 cases and 100 controls. The first SNP had mutant-allele frequency of .2; the other five SNPs were generated independently of the first by sampling five-SNP haplotypes with frequencies similar to those given in table 5 of Bugawan et al. (2003). Under model Null I, none of the SNPs were associated with disease. Under Null II, each mutant allele for the first SNP doubles disease risk, but the remaining five SNPs are not associated with disease. The multiple-comparisons procedures are applied to the p values from five Wald tests for interaction based on the logistic model Pr(disease)=α+β₁SNP₁+βSNP_i+β_intSNP^*₁SNP_i, analogous to that of Bugawan et al. (2003).

^a“CDF” denotes the cumulative distribution function procedure used by Bugawan et al. (2003); “Simes” is the standard Simes’s test; “RSimes” is Simes’s test applied to p values calculated by comparing the observed p values to the distribution of p values generated by permuting the outcome variable 200 times; “BHD” is the Benjamini and Hochberg step-up procedure corrected for general dependency (Benjamini and Yekutieli 2001) (the usual step-up procedure is identical to Simes’s test in this case); and “DRW” is the related procedure proposed by Devlin et al. (2003).