Supplemental Table 1: Type I error rates for gene set

Supplemental Table 1: Type I error rates for gene set methods. The two-step methods are named as a combination of two methods, the first indicating the method used to summarize SNPs to the gene and the second representing the method used to summarize the gene-level p-values to the gene set. Note that for approaches that don’t use the GM, the STT value is not applicable. STT Value Reduced LD (r2) Gene Set 2-Step GMRE-GM TRUE 0.6 TRUE 0.9 FALSE 0.6 FALSE 0.9 Type

2-Step

Method

PC-GM

NA

0.15

0.05

0.1

0.05 0.052 0.049 0.047

0.051 0.051 0.052 0.052

0.056 0.06 0.06 0.054 0.057 0.055 0.058 0.056 0.052 0.051 0.047 0.045 0.047 0.046 0.048 0.053

0.046 0.059 0.053 0.052

0.049 0.063 0.048 0.054

0.051 0.058 0.048 0.053

0.2

1/e*

0.01

TRUE TRUE FALSE FALSE

0.6 0.9 0.6 0.9

0.051 0.06 0.051 0.062

2-Step GMFE-GM

TRUE TRUE FALSE FALSE

0.6 0.9 0.6 0.9

0.052 0.054 0.052 0.048 0.052 0.058 0.06 0.064 0.057 0.053 0.047 0.047 0.046 0.046 0.044 0.06 0.063 0.06 0.054 0.059

2-Step

MinP-GM

TRUE TRUE FALSE FALSE

0.6 0.9 0.6 0.9

0.045 0.048 0.046 0.047

0.053 0.058 0.045 0.062

0.048 0.049 0.05 0.046 0.065 0.059 0.054 0.058 0.045 0.05 0.05 0.053 0.063 0.06 0.056 0.049

1-Step

GM

TRUE TRUE FALSE FALSE

0.6 0.9 0.6 0.9

0.048 0.049 0.049 0.049

0.053 0.053 0.059 0.056

0.051 0.058 0.052 0.058

1-Step

PC

TRUE TRUE FALSE FALSE

0.6 0.9 0.6 0.9

0.052 0.066 0.06 0.061

1-Step

GMRE

TRUE TRUE FALSE FALSE

0.6 0.9 0.6 0.9

0.049 0.049 0.048 0.052

0.055 0.053 0.051 0.061

0.051 0.049 0.058 0.056 0.048 0.05 0.051 0.049

0.054 0.055 0.055 0.056

0.049 0.059 0.048 0.063

0.049 0.055 0.051 0.055

PC = principal component analysis (based on 80% of the variation explained); GMRE = global model with random effects; GMFE = global model with fixed effects; MinP = SNP with the minimum p-value represents the gene-level effect. *GM with STT = 1/e is equivalent to Fisher’s method.