To account for the correlated tests from the determination of a genetic model for a given SNP and for the multiple correlated tests from the SNPs within each gene region, we performed a P-value adjustment for correlated tests. Specifically, the tests statistics are modeled as an asymptotically distributed multivariate normal with a co-variance structure estimated from the correlation of observed SNPs (82). This adjustment was performed first on the test statistics obtained by modeling dominant and additive genetic models for each SNP. The resulting adjusted P-values were then further adjusted to account both for the correlation and the number of tests performed across the SNPs within a gene region. The final adjusted P-value is reported and was used to rank the SNPs. System-level significance is determined using a Bonferroni correction across the 54 gene regions. Thus, for a family-wise or system-wide α-level we use 0.05/54 = 0.0009.
