This approach allows us to nominate candidate causal genes in eleven genome-wide significant and five suggestive AD risk loci, including TP53INP1, APBB3, RABEP1, and SPPL2A. In our second approach, we use Summary data-based Mendelian Randomization (SMR)14 to investigate the causal relationship between chromatin activity, target gene expression, and AD risk modification. Here, SPPL2A is linked to Alzheimer disease.