To identify genes whose mRNA expression or alternative splicing is associated with Alzheimer’s disease and mediated by genetic variation, we performed two Transcriptome-wide association studies (TWAS)37 by using either the ROSMAP expression data or its intronic excision levels as reference panels to re-analyze summary level data from the International Genomics of Alzheimer’s Project (IGAP) GWAS14. A total of 4,746 genes and 15,013 differentially spliced introns could be analyzed, and we identified 21 genes at FDR < 0.05 whose imputed gene expression or intronic excision levels were significantly associated with Alzheimer’s disease status (Fig. 5a; Supplementary Table 11). Among these, there were genes in known Alzheimer’s disease loci including SPI1, CR1, PTK2B, CLU, MTCH2, and PICALM. These results help to pinpoint the likely gene that is the target of the known susceptibility variant in each locus, particularly at the MTCH2 locus in which the functional consequence of the risk allele was unclear. However, the new Alzheimer’s disease genes are even more interesting, and 8 of these associations are found in loci that harbored only suggestive evidence of association in the IGAP
