Discovery of 40 risk loci does not equate to the discovery of 40 risk genes. Many susceptibility loci in Alzheimer’s disease are annotated as the nearest gene to the lead SNP. Furthermore, different studies have identified different lead SNPs and sometimes report different nearest genes within the same loci, such as 7q22.1 for which the closest genes identified across the four studies were PILRA, ZCWPW1, and NYAP1 (table 1). However, only about a third of trait–associated genes are the nearest gene.31 There are 1343 protein–coding genes within the 1 MB cis–regulatory region for gene expression across the 40 risk loci (table 1). As such, mapping of SNPs to the nearest gene can be false, and might result in incorrect assumptions about the relevant molecular pathways underlying disease. Consequently, genetic research is now moving from identification of loci associated with diseases to determination of function and causation.32–34
