In addition, improving SNP coverage and, thus, the number of informative genes may also be beneficial, although it will also increase the computational burden. Holmans et al. [31] performed an imputation analysis for un-typed SNPs using genotype information from the HapMap samples. They demonstrated that the imputation analysis could improve the power for detecting bipolar disorder (BPD) associated gene sets using their ALIGATOR method. Better refined gene set definitions [67,68] that group genes according to well-defined biological information may also be beneficial. For example, Low et al. [67] divided the estrogen metabolic pathway into three sub-pathways involved in androgen synthesis, androgen-to-estrogen conversion and estrogen removal and then found only SNPs within the androgen-to-estrogen conversion pathway were significantly associated with breast and endometrial cancer susceptibilities.
