Over twenty-four genetic loci have now been associated with Alzheimer’s disease susceptibility by Genome-wide Association Studies (GWAS)14, and these variants are enriched for associations with gene expression levels in peripheral myeloid cells and often lie within cis-regulatory elements15. For example, we reported that one of these variants influences splicing of CD3316. Given the high abundance of alternative splicing in the brain, we hypothesized that other Alzheimer’s disease-associated genetic variants might also affect pre-mRNA splicing, possibly by disrupting efficient binding of splicing factors.
