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Dementia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Identifying pleiotropy for blood pressure (BP) and cognitive performance measures may indicate mechanistic links between hypertension and Alzheimer's disease (AD).<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n We performed a pleiotropy genome\u2010wide association study (GWAS) for paired measures of systolic, diastolic, pulse, and mean arterial pressure with memory, executive function, and language scores using 116,075 exam data from 25,726 participants in clinic\u2010based and prospective cohorts. Significant findings were evaluated by Bayesian colocalization and differential gene expression in brain tissue from pathologically confirmed AD cases with and without clinical symptoms.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Genome\u2010wide significant pleiotropy for BP and cognitive performance with\n JPH2<\/jats:italic>\n ,\n GATA3<\/jats:italic>\n ,\n PAX2<\/jats:italic>\n ,\n LOC105371656<\/jats:italic>\n , and\n SUFU<\/jats:italic>\n in the total sample;\n RTN4<\/jats:italic>\n ,\n ULK2<\/jats:italic>\n ,\n SORBS2<\/jats:italic>\n , and\n LOC100128993<\/jats:italic>\n in prospective cohorts; and\n ADAMTS3<\/jats:italic>\n and\n LINC02946<\/jats:italic>\n in clinic\u2010based cohorts. Six pleiotropic loci influence cognition directly, and six genes were differentially expressed between pathologically confirmed AD cases with and without antemortem cognitive impairment.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n Our results provide insight into mechanisms underlying hypertension and AD.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n \n Genome\u2010wide significant pleiotropy in blood pressure (BP) and cognitive performance measures were identified with 11 novel loci:\n JPH2<\/jats:italic>\n ,\n GATA3<\/jats:italic>\n ,\n PAX2<\/jats:italic>\n ,\n LOC105371656<\/jats:italic>\n ,\n SUFU<\/jats:italic>\n in the total sample;\n RTN4<\/jats:italic>\n ,\n ULK2<\/jats:italic>\n ,\n SORBS2<\/jats:italic>\n ,\n LOC100128993<\/jats:italic>\n in prospective cohorts; and\n ADAMTS3<\/jats:italic>\n ,\n LINC02946<\/jats:italic>\n in clinic\u2010based cohorts.\n <\/jats:p>\n <\/jats:list-item>\n \n \n SUFU<\/jats:italic>\n ,\n RTN4<\/jats:italic>\n ,\n SORBS2<\/jats:italic>\n ,\n ADAMTS3<\/jats:italic>\n , and\n GATA3<\/jats:italic>\n affected cognition directly rather than through BP.\n <\/jats:p>\n <\/jats:list-item>\n \n \n ACTR1A<\/jats:italic>\n ,\n HIF1AN<\/jats:italic>\n ,\n ADAMTS3<\/jats:italic>\n ,\n RTN4<\/jats:italic>\n ,\n SORBS2<\/jats:italic>\n , and\n SUFU<\/jats:italic>\n at pleiotropic loci were differentially expressed among controls and pathologically confirmed AD cases with and without clinical symptoms.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70681","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T11:42:11Z","timestamp":1757936531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genome\u2010wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance 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