{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:22:28Z","timestamp":1781662948129,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":94,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp; Dem Diag Ass &amp; Dis Mo"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Genome\u2010wide association studies (GWAS) in late onset Alzheimer's disease (LOAD) provide lists of individual genetic determinants. However, GWAS do not capture the synergistic effects among multiple genetic variants and lack good specificity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied tree\u2010based machine learning algorithms (MLs) to discriminate LOAD (&gt;700 individuals) and age\u2010matched unaffected subjects in UK Biobank with single nucleotide variants (SNVs) from Alzheimer's disease (AD) studies, obtaining specific genomic profiles with the prioritized SNVs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MLs prioritized a set of SNVs located in genes\n                      <jats:italic>PVRL2<\/jats:italic>\n                      ,\n                      <jats:italic>TOMM40<\/jats:italic>\n                      ,\n                      <jats:italic>APOE<\/jats:italic>\n                      , and\n                      <jats:italic>APOC1<\/jats:italic>\n                      , also influencing gene expression and splicing. The genomic profiles in this region showed interaction patterns involving rs405509 and rs1160985, also present in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. rs405509 located in\n                      <jats:italic>APOE<\/jats:italic>\n                      promoter interacts with rs429358 among others, seemingly neutralizing their predisposing effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our approach efficiently discriminates LOAD from controls, capturing genomic profiles defined by interactions among SNVs in a hot\u2010spot region.<\/jats:p>\n                  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