For the gene-based analysis, we used the open-source tool: Knowledge-Based Mining System for Genome-Wide Genetic Studies (KGG, version 2.0)—based on the SNP association test results and LD files produced by PLINK. The procedure was performed as the following. We first calculate the effective number m e of independent P value among m SNPs within a gene. Then, we sort the SNPs and calculate the effective number m e(j) of independent P-values among the top j significant SNPs. Finally, the modified Simes test [51] was employed to obtain a gene-based P value as follows, (1)PG=Min(meP(j)me(j)), where P (j) is the jth most significant among the m SNPs within a gene. We refer the interested readers to [51] for details.
