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Dementia"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Although large\u2010scale genome\u2010wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We conducted a cross\u2010ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non\u2010Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene\u2010level analysis, we found novel genes for memory decline on chromosomes 1 (<jats:italic>SLC25A44<\/jats:italic>), 11 (<jats:italic>BSX<\/jats:italic>), and 15 (<jats:italic>DPP8<\/jats:italic>). Memory performance and memory decline shared genetic architecture with AD\u2010related traits, neuropsychiatric traits, and autoimmune traits.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>We discovered several novel loci, genes, and genetic correlations associated with late\u2010life memory performance and decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Late\u2010life memory has high heritability that is similar across ancestries.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We discovered four novel variants associated with late\u2010life memory.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We identified four novel genes associated with late\u2010life memory.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Late\u2010life memory shares genetic architecture with psychiatric\/autoimmune traits.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13508","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T17:39:20Z","timestamp":1700588360000},"page":"1268-1283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Derek B.","family":"Archer","sequence":"first","affiliation":[{"name":"Vanderbilt Memory &amp; Alzheimer's Center Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Genetics Institute Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn M.","family":"Eissman","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory &amp; Alzheimer's Center Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Genetics Institute Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhabrata","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo\u2010Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe","family":"Scollard","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily H.","family":"Trittschuh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine  Seattle Washington USA"},{"name":"VA Puget Sound Health Care System GRECC  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse B.","family":"Mez","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Bush","sequence":"additional","affiliation":[{"name":"Cleveland Institute for Computational Biology Department of Population and Quantitative Health Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"Kunkle","sequence":"additional","affiliation":[{"name":"John P. 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