While only an approximate representation of the underlying complexity of AD genetic mechanisms, our integrated phenotypic approaches successfully identified novel genetic variants that significantly associate with these composite AD phenotypes. The results were generally the same whether analyzing individual SNPs or genes. In the CC model, we identified a novel genome-wide association within an uncharacterized non-coding RNA locus LOC152225 on chromosome 3q12.3. We found no extant reports for this locus in PubMed or the NHGRI Catalogue of Published GWAS (www.genome.gov/gwastudies/). In the FS model, we detected genome-wide significant associations at SNPs in three genes within a large LD block on chromosome 2p21, each of which has reported expression in brain: (1) SLC3A1 encoding the large subunit of a heterodimeric dibasic /neutral amino acid transporter (solute carrier family 3 (amino acid transporter heavy chain), member 1); (2) PREPL encoding a putative prolyl endopeptidase belonging to the prolyl oligopeptidase family; and (3) CAMKMT encoding a calmodulin-lysine N-methyltransferase. This region is well-known for two contiguous gene-deletion syndromes, the hypotonia-cystinuria syndrome and the more severe 2p21 deletion syndrome (29). Deletion of SLC3A1 results in
