While we identify functionally relevant SNPs that are associated with the risk of AD and associated phenotypes, and demonstrate the utility of a parallel assay for functional SNPs, our study has several limitations. One limitation is that the SNPs tested in this study were not themselves genome-wide significant. Another is that we only screened the variants in 3’UTR; obviously, variants in other regulatory regions likely play a role in influencing the risk for AD and related phenotypes, and similar types of assays could be developed for those. Gene expression in any cell line depends both upon the unique genetics of that cell line and the exact culture conditions, which affect the expression of trans-acting factors. Many of the SNPs showed effects in the same direction, which is not unexpected since both cell lines are neuronal and presumably share many trans-acting factors. Those that differ in direction (or function in one cell line or the other) are presumably affected by a difference between the cell lines in the balance of trans-acting factors. Our use of 2 distinct cell lines provides a
