A test statistic can be constructed with units based on either gene or SNP association signals. We refer to them as gene-based and SNP-based methods, respectively. In the former, the P-values of the SNPs located within each gene are summarized by gene-level association measures first, and, then, the gene-level P-values are used to calculate gene set test scores. The power of these methods mainly depends on the proportion of the genes (for gene-based methods) or SNPs (for SNP-based methods) with strong association signals in the gene set. In practice, several studies reported gene-based methods may have more power [5,37]; this is because only a few SNPs, which are often located on different genes, may contribute to disease risk (or are in LD with causal variants).
