from a GWAS study, to examine the genetic etiology of AD in the Molecular Genetics of Schizophrenia Control Sample. Although no SNPs survived multiple testing corrections, Kendler et al. identified six genes in the European American sample and five genes in the African American sample that met the criteria for gene-wise significance using Plink, as well as a large number of enriched categories/pathways in Europeans (up to 347) and African Americans (up to 254). The advantage of pathway-enriched approaches is that they overcome the issue of genetic heterogeneity, which greatly reduces the power to detect an association. Thus, by shifting attention to the frequency of occurrence of variants related to a pathway, pathway-enriched approaches improve the power to detect an association. Similar pathway/enrichment approaches include: GenGen (http://www.openbioinformatics.org/gengen/; Wang et al., 2007), GSEA (for RNA expression analysis; http://www.broadinstitute.org/gsea/index.jsp; Subramanian et al., 2007, 2005), the SNP-ratio test (http://sourceforge.net/projects/snpratiotest/; O’Dushlaine et al., 2009), and INRICH (can be used for combinations of SNPs, CNVs, genes; http://atgu.mgh.harvard.edu/inrich/; Lee et al., 2012), to name a few. It is important to note however that pathway approaches are limited to existing knowledge about a gene and the biological pathways relevant to the disease. Furthermore, study results may not
