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Current treatments \u2013 repurposed from psychiatric disorders despite limited understanding of etiologic overlap \u2013 are often ineffective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      To characterize the genetic overlap between AD and major psychiatric disorders and identify shared molecular pathways, we conducted genetic correlation analyses between AD and depression, schizophrenia, bipolar disorder, and anxiety using MiXeR and Local\u00a0Analysis of [co]Variant\u00a0Annotation with genome wide association studies (GWAS) summary statistics (AD:\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0487,511; bipolar disorder:\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0413,466; depression:\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01,154,267; schizophrenia:\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0130,644; anxiety:\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01,096,458).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Local genetic correlation analyses followed by fine mapping and functional analyses identified a missense variant in\n                      <jats:italic>TMEM106B<\/jats:italic>\n                      (rs3173615) shared between AD and depression and anxiety, a regulatory region variant in\n                      <jats:italic>ACE<\/jats:italic>\n                      (rs4292) shared between AD\/schizophrenia, and two nonsense\u2010mediated mRNA decay transcript variants in\n                      <jats:italic>ERC2<\/jats:italic>\n                      (rs17288728; rs815460) shared between AD\/anxiety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The specific molecular pathways associated with these variants provide critical information on shared etiologic components underlying these traits and inform development of improved therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71278","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:36:36Z","timestamp":1773394596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic correlation analysis identifies\n                    <i>TMEM106B<\/i>\n                    ,\n                    <i>ACE<\/i>\n                    , and\n                    <i>ERC2<\/i>\n                    as genetic loci shared between Alzheimer's disease and primary psychiatric disorders"],"prefix":"10.1002","volume":"22","author":[{"given":"Ajneesh","family":"Kumar","sequence":"first","affiliation":[{"name":"Gertrude H. 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Sergievsky Center Columbia University  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela Del","family":"Rosario","sequence":"additional","affiliation":[{"name":"Gertrude H. Sergievsky Center Columbia University  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masood","family":"Manoochehri","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa N.","family":"De Vito","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna","family":"Cholerton","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Sweet","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Neurology School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil L.","family":"de Jager","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"},{"name":"Department of Neurology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Ulrich","family":"Klein","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"},{"name":"Department of Neurology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Cuccaro","sequence":"additional","affiliation":[{"name":"The John P. 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