Evidence map›Paper›PMID 40676597›Full record

SynthesisGenome biology2025

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

Farid Rajabli, Penelope Benchek, Giuseppe Tosto, Nicholas Kushch, Jin Sha, Katrina Bazemore, Congcong Zhu, Wan-Ping Lee, Jacob Haut, Kara L Hamilton-Nelson and 277 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. 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 · 2026
    Observational
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  5. Alzheimer's disease biological domain sub-stratification enhances the precision of functional analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

287 authors.

Farid Rajabli *Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Penelope Benchek *Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Giuseppe Tosto *Taub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Nicholas KushchThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Jin ShaDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katrina BazemoreDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Congcong ZhuDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Wan-Ping LeePenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jacob HautDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kara L Hamilton-NelsonThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Nicholas R WheelerDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Yi ZhaoPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John J FarrellDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Michelle A GruninDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Yuk Yee LeungPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Pavel P KuksaPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Donghe LiDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Eder Lucio da FonsecaThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Jesse B MezDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Ellen L PalmerDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Jagan PillaiCleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH, USA.
Richard M ShervaDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Yeunjoo E SongDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Xiaoling ZhangDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Takeshi IkeuchiMolecular Genetics Division, Brain Research Institute, Niigata University, Niigata, Japan.
Taha IqbalDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Omkar PathakPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Otto ValladaresPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dolly Reyes-DumeyerTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Amanda B KuzmaPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Erin AbnerSanders-Brown Center on Aging, Department of Epidemiology, College of Public Health, University of Kentucky, Lexington, KY, USA.
Larry D AdamsDr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Perrie M AdamsDepartment of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Alyssa AguirreDepartment of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
Marilyn S AlbertDepartment of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Roger L AlbinDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Mariet AllenDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Lisa AlvarezDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
Liana G ApostolovaDepartments of Neurology, Radiology, and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Steven E ArnoldDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sanjay AsthanaGeriatric Research, Education and Clinical Center (GRECC), University of Wisconsin, Madison, WI, USA.
Craig S AtwoodGeriatric Research, Education and Clinical Center (GRECC), University of Wisconsin, Madison, WI, USA.
Sanford AuerbachDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Gayle AyresDepartment of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
Clinton T BaldwinDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Robert C BarberDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
Lisa L BarnesDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Sandra BarralTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Thomas G BeachCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Phoenix, AZ, USA.
James T BeckerDepartments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine, Pennsylvania, WA, USA.
Gary W BeechamThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Duane BeeklyNational Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA.
Bruno A BenitezDepartment of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MO, USA.
David BennettDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
John BertelsonDepartment of Psychiatry , University of Texas at Austin/Dell Medical School, Austin, TX, USA.
Thomas D BirdVA Puget Sound Health Care System/GRECC, Seattle, WA, USA.
Deborah BlackerDepartment of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
James D BowenSwedish Medical Center, Seattle, WA, USA.
Adam BoxerDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
James BrewerDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
James R BurkeDepartment of Medicine, Duke University, Durham, NC, USA.
Jeffrey M BurnsUniversity of Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas City, KS, USA.
Joseph D BuxbaumDepartment of Genetics and Genomic Sciences, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nigel J CairnsDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.
Laura B CantwellPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Chuanhai CaoUSF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Christopher S CarlsonFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Cynthia M CarlssonDepartment of Medicine, University of Wisconsin, Madison, WI, USA.
Regina M CarneyMental Health and Behavioral Science Service, Bruce W. Carter VA Medical Center, Miami, FL, USA.
Minerva M CarrasquilloDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Scott ChasseDepartment of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA.
Marie-Francoise ChesseletNeurogenetics Program, University of California Los Angeles, Los Angeles, CA, USA.
Nathaniel A ChinGeriatric Research, Education and Clinical Center (GRECC), University of Wisconsin, Madison, WI, USA.
Helena C ChuiUniversity of California Los Angeles, University of Southern California, Los Angeles, CA, USA.
Jaeyoon ChungDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Suzanne CraftSection of Gerontology and Geriatric Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Paul K CraneDepartment of Medicine, University of Washington, Seattle, WA, USA.
David H CribbsDepartment of Neurology, University of California Irvine, Irvine, CA, USA.
Elizabeth A CroccoDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
Carlos CruchagaNeuroGenomics and Informatics, Washington University, St Louis, MO, USA.
Michael L CuccaroDr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Munro CullumDepartment of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Eveleen DarbyAlzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
Barbara DavisDepartment of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Charles DeCarliDepartment of Neurology, University of California Davis, Sacramento, CA, USA.
John DeToledoDepartments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Malcolm DickInstitute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Beth A DombroskiPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rachelle S DoodyAlzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
Ranjan DuaraWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA.
NIlüfer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Denis A EvansRush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
Kelley M FaberDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.
Thomas J FairchildOffice of Strategy and Measurement, University of North Texas Health Science Center, Fort Worth, TX, USA.
Kenneth B FallonDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
David W FardoSanders-Brown Center on Aging, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.
Martin R FarlowDepartment of Neurology, Indiana University, Indianapolis, IN, USA.
Victoria Fernandez-HernandezDepartment of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MO, USA.
Steven FerrisDepartment of Psychiatry, New York University, New York, NY, USA.
Robert P FriedlandDepartment of Neurology, University of Louisville School of Medicine, Lousiville, KY, USA.
Tatiana M ForoudDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.
Matthew P FroschC.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown, MA, USA.
Brian Fulton-HowardDepartment of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Douglas R GalaskoDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Adriana GamboaDepartment of Health Behavior and Health Systems, University of North Texas Health Science Center, Fort Worth, TX, USA.
Marla GearingDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
Daniel H GeschwindNeurogenetics Program, University of California Los Angeles, Los Angeles, CA, USA.
Bernardino GhettiDepartment of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA.
John R GilbertDr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Rodney C P GoDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Alison M GoateDepartment of Genetics and Genomic Sciences, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Thomas J GrabowskiDepartment of Neurology, University of Washington, Seattle, WA, USA.
Neill R Graff-RadfordDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Robert C GreenDivision of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Division of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Boston, MA, USA.
John H GrowdonDepartment of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Hakon HakonarsonCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
James HallDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
Ronald L HamiltonDepartment of Pathology (Neuropathology), University of Pittsburgh, Pittsburgh, PA, UK.
Oscar HarariDepartment of Psychiatry, Washington University in St. Louis, St Louis, MO, USA.
John HardyUCL Institute of Neurology, University College London, London, England, USA.
Lindy E HarrellDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA.
Victor W HendersonDepartment of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.
Michelle HernandezDepartments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Timothy HohmanVanderbilt Memory and Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Lawrence S HonigTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Ryan M HuebingerDepartment of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Matthew J HuentelmanNeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
Christine M HuletteDepartment of Pathology, Duke University, Durham, NC, USA.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Linda S HynanDepartment of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Gail P JarvikDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Suman JayadevDepartment of Neurology, University of Washington, Seattle, WA, USA.
Lee-Way JinDepartment of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA.
Kim JohnsonDepartments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Leigh JohnsonDepartment of Health Behavior and Health Systems, University of North Texas Health Science Center, Fort Worth, TX, USA.
M Ilyas KambohDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Anna M KarydasDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Mindy J KatzDepartment of Neurology, Albert Einstein College of Medicine, New York, NY, USA.
John S KauweDepartment of Neuroscience, Brigham Young University, Provo, UT, USA.
Jeffrey A KayeDepartment of Neurology, Oregon Health and Science University, Portland, OR, USA.
C Dirk KeeneDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Aisha KhaleeqAlzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
Masataka KikuchiMolecular Genetics Division, Brain Research Institute, Niigata University, Niigata, Japan.
Ronald KimDepartment of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA.
Janice KneblDepartment of Health Behavior and Health Systems, University of North Texas Health Science Center, Fort Worth, TX, USA.
Neil W KowallDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Joel H KramerDepartment of Neuropsychology, University of California San Francisco, San Francisco, CA, USA.
Walter A KukullDepartment of Epidemiology, University of Washington, Seattle, Seattle, USA.
Frank M LaFerlaDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
James J LahDepartment of Neurology, Emory University, Atlanta, GA, USA.
Eric B LarsonNational Center for PTSD, Boston VA Healthcare System, Boston, MA, USA.
Alan LernerDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
James B LeverenzCleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH, USA.
Allan I LeveyDepartment of Neurology, Emory University, Atlanta, GA, USA.
Andrew P LiebermanDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Richard B LiptonDepartment of Neurology, Albert Einstein College of Medicine, New York, NY, USA.
Mark LogueDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Oscar L LopezDepartments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine, Pennsylvania, WA, USA.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Constantine G LyketsosDepartment of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
Douglas MainsDepartment of Health Behavior and Health Systems, University of North Texas Health Science Center, Fort Worth, TX, USA.
Flanagan E MargaretDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Daniel C MarsonDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
Eden Rr MartinDr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Frank MartiniukDepartment of Medicine - Pulmonary, New York University, New York, NY, USA.
Deborah C MashDepartment of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Eliezer MasliahDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Paul MassmanAlzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
Arjun MasurkarDepartment of Psychiatry, New York University, New York, NY, USA.
Wayne C McCormickDepartment of Medicine, University of Washington, Seattle, WA, USA.
Susan M McCurrySchool of Nursing Northwest Research Group on Aging, University of Washington, Seattle, WA, USA.
Andrew N McDavidFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Stefan McDonoughPfizer Worldwide Research and Development, New York, NY, USA.
Ann C McKeeDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Marsel MesulamDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Bruce L MillerWeill Institute for Neurosciences, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
Carol A MillerDepartment of Pathology, University of Southern California, Los Angeles, CA, USA.
Joshua W MillerDepartment of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA.
Thomas J MontineDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Edwin S MonukiDepartment of Pathology and Laboratory Medicine and Alzheimer's Disease Research Center, University of California Irvine, Irvine, CA, USA.
John C MorrisDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.
Shubhabrata MukherjeeDepartment of Medicine, University of Washington, Seattle, WA, USA.
Amanda J MyersDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
Trung NguyenDepartment of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Thomas ObisesanDepartment of Research Regulatory Compliance, College of Medicine, Howard Unviersity, Washington, DC, USA.
Sid O'BryantInstitute for Translational Research, University of North Texas Health Science Center, Fort Worth,, TX, USA.
John M OlichneyCenter for Mind and Brain and Department of Neurology, University of California Davis, Sacramento, CA, USA.
Marcia OryCenter for Population Health and Aging, Texas AandM University Health Science Center, Lubbock , TX, USA.
Raymond PalmerDepartment of Family and Community Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Joseph E ParisiDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Henry L PaulsonDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Valory PavlikAlzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
David PaydarfarDepartment of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
Victoria PerezDepartments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Elaine PeskindDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Helen PetrovitchPacific Health Research & Education Institute, VA Pacific Islands Healthcare System, Honolulu, HI, USA.
Aimee PierceDepartment of Neurology, University of California Irvine, Irvine, CA, USA.
Marsha PolkDepartment of Family and Community Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Wayne W PoonInstitute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Huntington PotterDepartment of Neurology, University of Colorado School of Medicine, Aurora, CO, USA.
Liming QuPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mary QuicenoDepartment of Internal Medicine and Geriatrics, University of North Texas Health Science Center, Fort Worth, TX, USA.
Joseph F QuinnDepartment of Neurology, Oregon Health and Science University, Portland, OR, USA.
Ashok RajUSF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Murray RaskindDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Eric M ReimanNeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
Barry ReisbergDepartment of Psychiatry, New York University, New York, NY, USA.
Joan S ReischDepartment of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
John M RingmanDepartment of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
Erik D RobersonDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
Monica RodriguearAlzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada.
Howard J RosenDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Roger N RosenbergDepartment of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Donald R RoyallDepartments of Psychiatry, Medicine, Family and Community Medicine, and the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health Science Center at San Antonio,, San Antonio, TX, Canada.
Marwan SabbaghDepartment of Neurology, Barrow Neurological Institute St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
A Dessa SadovnickDepartment of Medical Genetics, University of British Columbia, Vancouver, Canada.
Mark A SagerDepartment of Medicine, University of Wisconsin, Madison, WI, USA.
Mary SanoDepartment of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
Andrew J SaykinDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.
Julie A SchneiderDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Lon S SchneiderUniversity of California Los Angeles, University of Southern California, Los Angeles, CA, USA.
William W SeeleyDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Susan H SliferThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Scott SmallTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Amanda G SmithUSF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Janet P SmithDepartment of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Joshua A SonnenDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Salvatore SpinaDepartment of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA.
Peter St George-HyslopCambridge Institute for Medical Research, University of Cambridge, Cambridge, England, USA.
Takiyah D StarksMaya Angelou Center for Health Equity, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Robert A SternDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Alan B StevensCenter for Applied Health Research, Baylor Scott & White Health, Temple, TX, USA.
Stephen M StrittmatterProgram in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA.
David SultzerDepartment of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
Russell H SwerdlowUniversity of Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas City, KS, USA.
Rudolph E TanziDepartment of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Jeffrey L TilsonRenaissance Computing Institute, University of North Carolina Chapel Hill, Chapel Hill, NC, USA.
John Q TrojanowskiPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Juan C TroncosoDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Magda TsolakiDepartment of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, USA.
Debby W TsuangVA Puget Sound Health Care System/GRECC, Seattle, WA, USA.
Vivianna M Van DeerlinPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Linda J van EldikSanders-Brown Center on Aging, Department of Neuroscience, College of Medicine, University of Kentucky, Kentucky, OH, USA.
Jeffery M VanceDr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Badri N VardarajanTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Robert VassarDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Harry V VintersDepartment of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
Jean-Paul VonsattelTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Sandra WeintraubDepartment of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Kathleen A Welsh-BohmerDepartment of Medicine, Duke University, Durham, NC, USA.
Patrice L WhiteheadThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Ellen M WijsmanDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Kirk C WilhelmsenDepartment of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA.
Benjamin WilliamsDepartment of Pathology, Oregon Health and Science University, Portland, OR, USA.
Jennifer WilliamsonTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Henrik WilmsDepartments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Thomas S WingoDepartment of Neurology, Emory University, Atlanta, GA, USA.
Thomas WisniewskiDepartment of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.
Randall L WoltjerDepartment of Pathology, Oregon Health and Science University, Portland, OR, USA.
Martin WoonDepartment of Psychiatry , University of Texas at Austin/Dell Medical School, Austin, TX, USA.
Clinton B WrightEvelyn F. McKnight Brain Institute, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Chuang-Kuo WuDepartments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Steven G YounkinDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Chang-En YuDepartment of Medicine, University of Washington, Seattle, WA, USA.
Lei YuWisconsin Alzheimer's Disease Research Center, Madison, WI, USA.
Xiongwei ZhuSocial Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Brian W KunkleDr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
William S BushDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Akinori MiyashitaMolecular Genetics Division, Brain Research Institute, Niigata University, Niigata, Japan.
Goldie S ByrdDepartment of Ophthalmology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Li-San WangPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lindsay A FarrerDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Richard MayeuxTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA.
Margaret A Pericak-VanceDr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Gerard D SchellenbergPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Gyungah R Jun *Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Christiane Reitz *Department of Neurology, Columbia University, New York, NY, USA.
Adam C Naj *Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. adamnaj@pennmedicine.upenn.edu.
Alzheimer’s Disease Genetics Consortium (ADGC)

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
Translational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI Linda Kathleen McEvoy · 2021 to 2026
$80.4M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS, Suzanne Elizabeth Schindler · 1985 to 2026
$69.5M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI MARIA LUISA GORNO TEMPINI · 2002 to 2026
$67.2M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EDLAND, STEVEN DYAL · 1985 to 2018
$55.4M
Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP)U19AG074865 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI GOLDIE S. BYRD, William S Bush · 2022 to 2026
$55.3M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI CIRRITO, JOHN R · 1985 to 2019
$52.1M
NCI NIH HHS R01 CA129769NCRR NIH HHS KL2 RR024151NCRR NIH HHS UL1 RR029893NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01 HG008657NIA NIH HHS P01 AG002219NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG026276NIA NIH HHS P01 AG060882NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028377NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG072976NIA NIH HHS P50 AG005128NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005144NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008671NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG016582NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS R01 AG009029NIA NIH HHS R01 AG009956NIA NIH HHS R01 AG012101NIA NIH HHS R01 AG013616NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017173NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG020688NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG022374NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG026916NIA NIH HHS R01 AG028786NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG031581NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG035137NIA NIH HHS R01 AG041232NIA NIH HHS R01 AG041718NIA NIH HHS R01 AG042437NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG054060NIA NIH HHS R01 AG064877NIA NIH HHS R01 AG067501NIA NIH HHS R01 AG070864NIA NIH HHS R01 AG072474NIA NIH HHS R01 AG072547NIA NIH HHS R01 AG082730NIA NIH HHS R56 AG064877NIA NIH HHS R56 AG074527NIA NIH HHS RC2 AG036502NIA NIH HHS RC2 AG036528NIA NIH HHS RC2 AG036650NIA NIH HHS RF1 AG057519NIA NIH HHS RF1 AG061351NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG052410NIA NIH HHS U01 AG057659NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG062943NIA NIH HHS U01 AG066767NIA NIH HHS U01 AG081230NIA NIH HHS U19 AG066567NIA NIH HHS U19 AG074865NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NIA NIH HHS U54 AG052427NIMHD NIH HHS P20 MD000546NIMH NIH HHS P50 MH060451NIMH NIH HHS R01 MH080295NINDS NIH HHS P50 NS039764NINDS NIH HHS R01 NS059873Wellcome Trust
6 · The paper itself

Abstract

backgroundLimited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis.

resultsWe identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14).

conclusionsUsing cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease.

Indexed as

Alzheimer DiseaseGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyBlack or African AmericanHispanic or LatinoHumansMalePolymorphism, Single NucleotideWhiteAlzheimer diseaseGenome-wide association study (GWAS)GWAS meta-analysis,Multi-ancestryPopulation-specific

Identifiers

PMID40676597
PMCPMC12273372

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