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We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      A genetic association study was conducted to examine ADAD AAO in 340 individuals with the\n                      <jats:italic>PSEN1 E280A<\/jats:italic>\n                      mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early\u2010onset AD study and four late\u2010onset AD studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      13 variants had\n                      <jats:italic>p<\/jats:italic>\n                      &lt;1\u00d710\n                      <jats:sup>\u22127<\/jats:sup>\n                      or\n                      <jats:italic>p<\/jats:italic>\n                      &lt;1\u00d710\n                      <jats:sup>\u22125<\/jats:sup>\n                      with replication including three independent loci with candidate associations with clusterin including near\n                      <jats:italic>CLU<\/jats:italic>\n                      . Other suggestive associations were identified in or near\n                      <jats:italic>HS3ST1<\/jats:italic>\n                      ,\n                      <jats:italic>HSPG2<\/jats:italic>\n                      ,\n                      <jats:italic>ACE<\/jats:italic>\n                      ,\n                      <jats:italic>LRP1B<\/jats:italic>\n                      ,\n                      <jats:italic>TSPAN10<\/jats:italic>\n                      , and\n                      <jats:italic>TSPAN14<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13021","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T07:01:46Z","timestamp":1679554906000},"page":"3835-3847","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic associations with age at dementia onset in the\n                    <i>PSEN1 E280A<\/i>\n                    Colombian kindred"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-5504","authenticated-orcid":false,"given":"Jesse Nicholas","family":"Cochran","sequence":"first","affiliation":[{"name":"HudsonAlpha Institute for Biotechnology  Huntsville Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Acosta\u2010Uribe","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute University of California, Santa Barbara, California, and Department of Molecular Cellular and Developmental Biology University of California  Santa Barbara California USA"},{"name":"Grupo de Neurociencias de Antioquia. School of Medicine. Universidad de Antioquia  Medell\u00edn Antioquia Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca T.","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Genetics &amp; Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Madrigal","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias de Antioquia. School of Medicine. Universidad de Antioquia  Medell\u00edn Antioquia Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Aguill\u00f3n","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias de Antioquia. School of Medicine. 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