ArticleNature genetics2026
A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.
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Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.Nature genetics · 2026Article
- Stratification by a polygenic risk score of common variation aids in Alzheimer's disease rare variant discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Observational
Corrections and comments
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Authors and funding
42 authors.
Nuzulul KurniansyahBioinformatics Program, Boston University, Boston, MA, USA.
Shinya TasakiRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-3656-7394
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.ORCID http://orcid.org/0000-0001-6502-1572
Richard ShervaDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2133-1493
Richard HaugerResearch Service, VA San Diego Healthcare System, San Diego, CA, USA.ORCID http://orcid.org/0000-0003-1509-1868
Victoria C MerrittResearch Service, VA San Diego Healthcare System, San Diego, CA, USA.ORCID http://orcid.org/0000-0001-5683-4168
Matthew PanizzonDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
Rui ZhangNational Center for PTSD, Behavioral Sciences Division, VA Boston Healthcare System, Boston, MA, 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.ORCID http://orcid.org/0000-0002-6454-9751
Kunho LeeBK21 FOUR, Department of Integrative Biological Sciences, Chosun University, Gwangju, Republic of Korea.ORCID http://orcid.org/0000-0003-4144-8162
Dong Yong LeeDepartment of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0001-8976-8320
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.ORCID http://orcid.org/0000-0003-3311-4197
Shubhabrata MukherjeeDepartment of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-2522-2884
Emily H TrittschuhGeriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
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 Hospital and the New York Presbyterian Hospital, New York, NY, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/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.
Eden MartinJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
William S BushDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-9729-6519
Richard MayeuxDepartment of Neurology, Columbia University Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-6519-9696
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, School of Medicine, 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.ORCID http://orcid.org/0000-0001-9347-7892
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, USA.ORCID http://orcid.org/0000-0002-3377-7014
Li-San WangDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Ting Fang Alvin AngDepartment of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4687-2552
Rhoda AuDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7742-4491
Jesse MezFramingham Heart Study, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1438-5442
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9268-810X
Xiaoling ZhangBioinformatics Program, Boston University, Boston, MA, USA. zhangxl@bu.edu.ORCID http://orcid.org/0000-0001-8237-1857
Lindsay A FarrerBioinformatics Program, Boston University, Boston, MA, USA. farrer@bu.edu.ORCID http://orcid.org/0000-0001-5533-4225
Funding
TBDU19AG068753 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Lindsay A. Farrer · 2020 to 2026
$42.4MThe Alzheimer Disease Sequence Analysis CollaborativeU01AG058654 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI BUSH, WILLIAM S, FARRER, LINDSAY A. · 2018 to 2022
$14.6MGenetic Studies of Alzheimer Disease in KoreansU01AG062602 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARRER, LINDSAY A. · 2019 to 2023
$9.5MAlzheimer Disease Genetic Architecture in African AmericansR01AG048927 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Lindsay A. Farrer · 2015 to 2026
$8.4MCircular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathologyU01AG072577 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WOLOZIN, BENJAMIN L, ZHANG, XIAOLING · 2021 to 2025
$3.8MThe role of N6-methyladenosine modified RNA in Alzheimer's disease: Equipment SupplementR01AG080810 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Benjamin L Wolozin, Xiaoling Zhang · 2023 to 2026
$3.2MAPOE Genotype Mediated Effects on Alzheimer Disease Risk and MechanismsU01AG082665 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Lindsay A. Farrer, Gyungah Jun · 2024 to 2026
$2.4MPredoctoral Training in Bioinformatics and Computational BiologyT32GM150533 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI GARY E. BENSON, Daniel Segre · 2023 to 2026
$1.3MNIA NIH HHS R01 AG048927NIA NIH HHS R01 AG080810NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG062602NIA NIH HHS U01 AG072577NIA NIH HHS U01 AG082665NIA NIH HHS U19 AG068753NIGMS NIH HHS T32 GM150533U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32-GM150533U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01-AG048927U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01-AG080810U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01-AG058654U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01-AG062602U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01-AG072577U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01-AG082665U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U19-AG068753
Abstract
Previously derived polygenic risk scores (PRSs) for Alzheimer's disease (AD) perform inconsistently across diverse ancestries. We developed an APOE-independent multiancestry AD PRS using genome-wide association study summary statistics applied to European ancestry, African American, Caribbean Hispanic and East Asian cohorts. PRS performance was evaluated in a large independent multiancestry dataset and validated in several additional multiancestry cohorts. The PRS was significantly associated with AD in European ancestry, African American, Caribbean Hispanic and Native American Hispanic groups with adjusted odds ratios between 1.14 and 1.52 per PRS standard deviation. PRS performance was validated in the replication cohorts (odds ratios: 1.21-1.65). The PRS was also associated with poorer memory, executive function and language performance, greater AD-related neuropathological burden, reduced hippocampal volume, lower cerebrospinal fluid amyloid-β
Indexed as
Alzheimer DiseaseCognitive DysfunctionGenetic Risk ScoreAgedAmyloid beta-PeptidesBlack or African AmericanCaribbean PeopleCohort StudiesEast Asian PeopleEuropean PeopleFemaleGenome-Wide Association StudyHispanic or LatinoHumansMalePolymorphism, Single NucleotideAmyloid beta-Peptidestau Proteins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.