ArticlemedRxiv : the preprint server for health sciences2025
A multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations.
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45 authors.
Nuzulul KurniansyahBioinformatics Program, Boston University, Boston, MA, USA.ORCID 0009-0002-5488-1600
Shinya TasakiRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Habbibur RehmanDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Congcong ZhuDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
John FarrellDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Richard ShervaDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Richard HaugerResearch Service, VA San Diego Healthcare System, San Diego, USA.
Victoria C MerrittResearch Service, VA San Diego Healthcare System, San Diego, USA.
Matthew PanizzonDepartment of Psychiatry, University of California, San Diego, La Jolla, USA.
Rui ZhangNational Center for PTSD, Behavioral Sciences Division, VA Boston Healthcare System, Boston, USA.
J Michael GazianoMillion Veteran Program (MVP) Coordinating Center, VA Boston Healthcare System, Boston, MA, USA.
Jungsoo GimBK21 FOUR, Department of Integrative Biological Sciences, Chosun University, Gwangju, Republic of Korea.
Kunho LeeBK21 FOUR, Department of Integrative Biological Sciences, Chosun University, Gwangju, Republic of Korea.
Dong Yong LeeDepartment of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kwansik NhoDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Ricardo A VialleRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Shubhabrata MukherjeeDepartment of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Emily H TrittschuhGeriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108.
Annie J LeeDepartment of Neurology, Columbia University Medical Center, New York, NY, USA.
Adam M BrickmanDepartment of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.ORCID 0000-0002-0276-2899
Shannon RisacherDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Douglas N GreveDepartment of Radiology, Massachusetts General Hospital, Boston, MA, USA.
Paul CraneDepartment of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
VA Million Veteran Program
Alzheimer’s Disease Genetics Consortium
Alzheimer Disease Sequencing Project
Eden MartinJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
William BushDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0002-9729-6519
Richard MayeuxDepartment of Neurology, Columbia University Medical Center, New York, NY, USA.ORCID 0000-0001-6519-9696
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Mark LogueDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Lisa L BarnesRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Andrew SaykinDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Timothy HohmanVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN.
Li-San WangDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Gerard C SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Ting Fang Alvin AngDepartment of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA.
Rhoda AuDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Jesse MezFramingham Heart Study, Boston University Chobanian & Avedisian School of Medicine, Boston, MA.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Xiaoling ZhangBioinformatics Program, Boston University, Boston, MA, USA.ORCID 0000-0001-8237-1857
Lindsay A FarrerBioinformatics Program, Boston University, Boston, MA, USA.
Funding
Technology to Empower Changes in Health (TECH) Network Participant Technologies CenterU24OD023176 · OD · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2016 to 2022
$204.7MPrecision Medicine Initiative Cohort Program BiobankU24OD023121 · OD · MAYO CLINIC ROCHESTER · PI CEKANOVA, MARIA, CICEK, MINE · 2016 to 2024
$185.5MThe Health & Aging Brain Study - Health Disparities (HABS-HD)U19AG078109 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI LEIGH A JOHNSON · 2022 to 2026
$181.1MEnhancing All of Us Data Resources for Nutrition Precision Health: the All of Us Data and Research CenterU2COD023196 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GLAZER, DAVID, HARRIS, PAUL A. · 2016 to 2022
$143.7MAdaptive Platform for Personalized EngagementU24OD023163 · OD · VIGNET, INC. · PI JAIN, PRADUMAN · 2017 to 2020
$102.6MUniversity of Arizona-Banner Health All of Us Research Program OT2OD026549 · OD · UNIVERSITY OF ARIZONA · PI MORENO, FRANCISCO A, REIMAN, ERIC MICHAEL · 2018 to 2023
$78.9MCalifornia Precision Medicine Research Program ConsortiumOT2OD026552 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANTON-CULVER, HODA A, OHNO-MACHADO, LUCILA · 2018 to 2023
$73.4MAll of Us PennsylvaniaOT2OD026554 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E, VISWESWARAN, SHYAM · 2018 to 2023
$72.1MNew York City Consortium for Precision MedicineOT2OD026556 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BIER, LOUISE E, GHARAVI, ALI G · 2018 to 2023
$67.3MSouthEast Enrollment Center (SEEC) OT2OD026551 · OD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CARRASQUILLO, OLVEEN, COLON, VIVIAN · 2018 to 2023
$62.8MSouthern All of Us NetworkOT2OD026548 · OD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FOUAD, MONA N., KORF, BRUCE R · 2018 to 2023
$60.5MIllinois Precision Medicine Consortium OT2OD026557 · OD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI AHSAN, HABIBUL, ARGOS, MARIA · 2018 to 2023
$60.5MBLRD VA I01 BX004192BLRD VA I01 BX005749NHLBI NIH HHS N01 HC025195NIA NIH HHS K01 AG084849NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072978NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG080810NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG062602NIA NIH HHS U01 AG072572NIA NIH HHS U01 AG072577NIA NIH HHS U01 AG082665NIA NIH HHS U19 AG068753NIA NIH HHS U19 AG078109NIGMS NIH HHS T32 GM150533NIH HHS OT2 OD023205NIH HHS OT2 OD023206NIH HHS OT2 OD025276NIH HHS OT2 OD025277NIH HHS OT2 OD025315NIH HHS OT2 OD025337NIH HHS OT2 OD026548NIH HHS OT2 OD026549NIH HHS OT2 OD026550NIH HHS OT2 OD026551NIH HHS OT2 OD026552NIH HHS OT2 OD026553NIH HHS OT2 OD026554NIH HHS OT2 OD026555NIH HHS OT2 OD026556NIH HHS OT2 OD026557NIH HHS U24 OD023121NIH HHS U24 OD023163NIH HHS U24 OD023176NIH HHS U2C OD023196
Abstract
Alzheimer disease (AD) has a strong genetic basis, yet previously derived polygenic risk scores (PRS) are heavily weighted by the
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