Here, by applying state-of-the-art analytic methods, we generated a comprehensive genome-wide map of splicing variation in the aging prefrontal cortex. We use this map to identify: (1) aberrant mRNA splicing events related to Alzheimer’s disease; (2) a new reference of thousands of genetic variants influencing local mRNA splicing in the brain; (3) trans acting splicing factors that are involved in intron excision; and (4) association of GWAS findings to specific genes within each Alzheimer’s disease susceptibility locus. Overall, we deepen our understanding of genetic regulation in the aging brain’s transcriptome and provide a foundation for the formulation of mechanistic hypotheses in Alzheimer’s disease and other neurodegenerative diseases.
