An Enhanced Multiple Correction Method with Limited Independent Effective SNPs

In genome-wide association studies (GWAS) and candidate gene studies (CGS), appropriate multiple testing correction methods can effectively address linkage disequilibrium (LD) blocks and are crucial for controlling the family-wise error rate (FWER) while ensuring the reliability of results. In our recent research, we observed that when the number of independent effective Single Nucleotide Polymorphisms (SNPs) is relatively small, existing multiple testing correction methods struggle to effectively control the FWER at 0.05 and lack robustness. This study proposes an enhanced method that builds upon the Moskvina and Schmidt approach by incorporating additional SNP correlation information, allowing for precise control of the FWER at 0.05 with limited independent effective SNPs. We also leverage Monte Carlo integration on a GPU to accelerate the computation of significance thresholds. Our method was evaluated through both simulation studies and real genotype datasets, demonstrating superior performance and robustness compared to existing methods.