Identifying partial haplotypes that are associated with late‐onset Alzheimer disease

The network model was created blindly using all individuals in the Discovery dataset, yet two of the clusters were significantly associated with AD risk in both the Discovery and Validation data. Interestingly, THOP1 is a zinc-activated oligopeptidase that is capable of cleaving beta-amyloid precursor protein into amyloidogenic peptides. Furthermore, SLC39A3 is predicted to enable zinc transport across the membrane, SGTA is suggested to play a role in aggregate formation in neurodegenerative diseases, and methylation of DIRAS1 is associated with AD risk. These results identify interesting signatures that may pinpoint specific AD biological pathways, motivating further validation efforts.