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Dementia"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether the extent of overlap of the genetic architecture among the sporadic late\u2010onset Alzheimer's Disease (sLOAD), familial late\u2010onset AD (fLOAD), sporadic early\u2010onset AD (sEOAD), and autosomal dominant early\u2010onset AD (eADAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Polygenic risk scores (PRSs) were constructed using previously identified 21 genome\u2010wide significant loci for LOAD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR]\u00a0=\u00a02.27;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a01.29\u00a0\u00d7\u00a010\n                      <jats:sup>\u22127<\/jats:sup>\n                      ) was observed in sEOAD, followed by fLOAD (OR\u00a0=\u00a01.75;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a01.12\u00a0\u00d7\u00a010\n                      <jats:sup>\u22127<\/jats:sup>\n                      ) and sLOAD (OR\u00a0=\u00a01.40;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a01.21\u00a0\u00d7\u00a010\n                      <jats:sup>\u22123<\/jats:sup>\n                      ). The PRS was associated with cerebrospinal fluid ptau\n                      <jats:sub>181<\/jats:sub>\n                      \u2010A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      on eADAD (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a04.36\u00a0\u00d7\u00a010\n                      <jats:sup>\u22122<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2017.08.013","type":"journal-article","created":{"date-parts":[[2017,9,21]],"date-time":"2017-09-21T21:30:25Z","timestamp":1506029425000},"page":"205-214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Polygenic risk score of sporadic late\u2010onset Alzheimer's disease reveals a shared architecture with the familial and early\u2010onset forms"],"prefix":"10.1002","volume":"14","author":[{"given":"Carlos","family":"Cruchaga","sequence":"first","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"},{"name":"Knight Alzheimer's Disease Research Center Washington University School of Medicine  St. Louis MO USA"},{"name":"Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L.","family":"Del\u2010Aguila","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Saef","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Victoria","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ibanez","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetiva","family":"Deming","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manav","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Ronald M. 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