Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures
  • Kang, Moonil
  • Ang, Ting Fang Alvin
  • Devine, Sherral A.
  • Sherva, Richard
  • Mukherjee, Shubhabrata
  • 외 22명
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초록

INTRODUCTION: Identifying pleiotropy for blood pressure (BP) and cognitive performance measures may indicate mechanistic links between hypertension and Alzheimer's disease (AD). METHODS: We performed a pleiotropy genome-wide 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-based 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. RESULTS: Genome-wide significant pleiotropy for BP and cognitive performance with JPH2, GATA3, PAX2, LOC105371656, and SUFU in the total sample; RTN4, ULK2, SORBS2, and LOC100128993 in prospective cohorts; and ADAMTS3 and LINC02946 in clinic-based cohorts. Six pleiotropic loci influence cognition directly, and six genes were differentially expressed between pathologically confirmed AD cases with and without antemortem cognitive impairment. DISCUSSION: Our results provide insight into mechanisms underlying hypertension and AD.

키워드

Alzheimer's diseaseblood pressurecognitive domain scoredifferential gene expressiongenome-wide association studylongitudinal studypathway analysispleiotropyCENTER NACC DATABASELD SCORE REGRESSIONALZHEIMERS-DISEASEPOPULATION-STRUCTUREGENETIC ASSOCIATIONRISK LOCILATE-LIFEMETAANALYSISDEMENTIAHYPERTENSION
제목
Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures
저자
Kang, MoonilAng, Ting Fang AlvinDevine, Sherral A.Sherva, RichardMukherjee, ShubhabrataTrittschuh, Emily H.Scollard, PhoebeLee, MichaelChoi, Seo EunKlinedinst, BrandonNakano, ConnieDumitrescu, Logan C.Hohman, Timothy J.Cuccaro, Michael L.Saykin, Andrew J.Kukull, Walter A.Bennett, David A.Wang, Li-SanMayeux, Richard P.Haines, Jonathan L.Pericak-Vance, Margaret A.Schellenberg, Gerard D.Crane, Paul K.Au, RhodaLunetta, Kathryn L.Mez, JesseFarrer, Lindsay A.
DOI
10.1002/alz.70681
발행일
2025-09
유형
Article
저널명
Alzheimer's and Dementia
21
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