Genome Biology (Jul 2025)
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,
- Nicholas R. Wheeler,
- Yi Zhao,
- John J. Farrell,
- Michelle A. Grunin,
- Yuk Yee Leung,
- Pavel P. Kuksa,
- Donghe Li,
- Eder Lucio da Fonseca,
- Jesse B. Mez,
- Ellen L. Palmer,
- Jagan Pillai,
- Richard M. Sherva,
- Yeunjoo E. Song,
- Xiaoling Zhang,
- Takeshi Ikeuchi,
- Taha Iqbal,
- Omkar Pathak,
- Otto Valladares,
- Dolly Reyes-Dumeyer,
- Amanda B. Kuzma,
- Erin Abner,
- Larry D. Adams,
- Perrie M. Adams,
- Alyssa Aguirre,
- Marilyn S. Albert,
- Roger L. Albin,
- Mariet Allen,
- Lisa Alvarez,
- Liana G. Apostolova,
- Steven E. Arnold,
- Sanjay Asthana,
- Craig S. Atwood,
- Sanford Auerbach,
- Gayle Ayres,
- Clinton T. Baldwin,
- Robert C. Barber,
- Lisa L. Barnes,
- Sandra Barral,
- Thomas G. Beach,
- James T. Becker,
- Gary W. Beecham,
- Duane Beekly,
- Bruno A. Benitez,
- David Bennett,
- John Bertelson,
- Thomas D. Bird,
- Deborah Blacker,
- Bradley F. Boeve,
- James D. Bowen,
- Adam Boxer,
- James Brewer,
- James R. Burke,
- Jeffrey M. Burns,
- Joseph D. Buxbaum,
- Nigel J. Cairns,
- Laura B. Cantwell,
- Chuanhai Cao,
- Christopher S. Carlson,
- Cynthia M. Carlsson,
- Regina M. Carney,
- Minerva M. Carrasquillo,
- Scott Chasse,
- Marie-Francoise Chesselet,
- Nathaniel A. Chin,
- Helena C. Chui,
- Jaeyoon Chung,
- Suzanne Craft,
- Paul K. Crane,
- David H. Cribbs,
- Elizabeth A. Crocco,
- Carlos Cruchaga,
- Michael L. Cuccaro,
- Munro Cullum,
- Eveleen Darby,
- Barbara Davis,
- Philip L. De Jager,
- Charles DeCarli,
- John DeToledo,
- Malcolm Dick,
- Dennis W. Dickson,
- Beth A. Dombroski,
- Rachelle S. Doody,
- Ranjan Duara,
- NIlüfer Ertekin-Taner,
- Denis A. Evans,
- Kelley M. Faber,
- Thomas J. Fairchild,
- Kenneth B. Fallon,
- David W. Fardo,
- Martin R. Farlow,
- Victoria Fernandez-Hernandez,
- Steven Ferris,
- Robert P. Friedland,
- Tatiana M. Foroud,
- Matthew P. Frosch,
- Brian Fulton-Howard,
- Douglas R. Galasko,
- Adriana Gamboa,
- Marla Gearing,
- Daniel H. Geschwind,
- Bernardino Ghetti,
- John R. Gilbert,
- Rodney C.P. Go,
- Alison M. Goate,
- Thomas J. Grabowski,
- Neill R. Graff-Radford,
- Robert C. Green,
- John H. Growdon,
- Hakon Hakonarson,
- James Hall,
- Ronald L. Hamilton,
- Oscar Harari,
- John Hardy,
- Lindy E. Harrell,
- Elizabeth Head,
- Victor W. Henderson,
- Michelle Hernandez,
- Timothy Hohman,
- Lawrence S. Honig,
- Ryan M. Huebinger,
- Matthew J. Huentelman,
- Christine M. Hulette,
- Bradley T. Hyman,
- Linda S. Hynan,
- Laura Ibanez,
- Gail P. Jarvik,
- Suman Jayadev,
- Lee-Way Jin,
- Kim Johnson,
- Leigh Johnson,
- M. Ilyas Kamboh,
- Anna M. Karydas,
- Mindy J. Katz,
- John S. Kauwe,
- Jeffrey A. Kaye,
- C. Dirk Keene,
- Aisha Khaleeq,
- Masataka Kikuchi,
- Ronald Kim,
- Janice Knebl,
- Neil W. Kowall,
- Joel H. Kramer,
- Walter A. Kukull,
- Frank M. LaFerla,
- James J. Lah,
- Eric B. Larson,
- Alan Lerner,
- James B. Leverenz,
- Allan I. Levey,
- Andrew P. Lieberman,
- Richard B. Lipton,
- Mark Logue,
- Oscar L. Lopez,
- Kathryn L. Lunetta,
- Constantine G. Lyketsos,
- Douglas Mains,
- Flanagan E. Margaret,
- Daniel C. Marson,
- Eden RR. Martin,
- Frank Martiniuk,
- Deborah C. Mash,
- Eliezer Masliah,
- Paul Massman,
- Arjun Masurkar,
- Wayne C. McCormick,
- Susan M. McCurry,
- Andrew N. McDavid,
- Stefan McDonough,
- Ann C. McKee,
- Marsel Mesulam,
- Bruce L. Miller,
- Carol A. Miller,
- Joshua W. Miller,
- Thomas J. Montine,
- Edwin S. Monuki,
- John C. Morris,
- Shubhabrata Mukherjee,
- Amanda J. Myers,
- Trung Nguyen,
- Thomas Obisesan,
- Sid O’Bryant,
- John M. Olichney,
- Marcia Ory,
- Raymond Palmer,
- Joseph E. Parisi,
- Henry L. Paulson,
- Valory Pavlik,
- David Paydarfar,
- Victoria Perez,
- Elaine Peskind,
- Ronald C. Petersen,
- Helen Petrovitch,
- Aimee Pierce,
- Marsha Polk,
- Wayne W. Poon,
- Huntington Potter,
- Liming Qu,
- Mary Quiceno,
- Joseph F. Quinn,
- Ashok Raj,
- Murray Raskind,
- Eric M. Reiman,
- Barry Reisberg,
- Joan S. Reisch,
- John M. Ringman,
- Erik D. Roberson,
- Monica Rodriguear,
- Ekaterina Rogaeva,
- Howard J. Rosen,
- Roger N. Rosenberg,
- Donald R. Royall,
- Marwan Sabbagh,
- A. Dessa Sadovnick,
- Mark A. Sager,
- Mary Sano,
- Andrew J. Saykin,
- Julie A. Schneider,
- Lon S. Schneider,
- William W. Seeley,
- Susan H. Slifer,
- Scott Small,
- Amanda G. Smith,
- Janet P. Smith,
- Joshua A. Sonnen,
- Salvatore Spina,
- Peter St George-Hyslop,
- Takiyah D. Starks,
- Robert A. Stern,
- Alan B. Stevens,
- Stephen M. Strittmatter,
- David Sultzer,
- Russell H. Swerdlow,
- Rudolph E. Tanzi,
- Jeffrey L. Tilson,
- John Q. Trojanowski,
- Juan C. Troncoso,
- Magda Tsolaki,
- Debby W. Tsuang,
- Vivianna M. Van Deerlin,
- Linda J. van Eldik,
- Jeffery M. Vance,
- Badri N. Vardarajan,
- Robert Vassar,
- Harry V. Vinters,
- Jean-Paul Vonsattel,
- Sandra Weintraub,
- Kathleen A. Welsh-Bohmer,
- Patrice L. Whitehead,
- Ellen M. Wijsman,
- Kirk C. Wilhelmsen,
- Benjamin Williams,
- Jennifer Williamson,
- Henrik Wilms,
- Thomas S. Wingo,
- Thomas Wisniewski,
- Randall L. Woltjer,
- Martin Woon,
- Clinton B. Wright,
- Chuang-Kuo Wu,
- Steven G. Younkin,
- Chang-En Yu,
- Lei Yu,
- Xiongwei Zhu,
- Brian W. Kunkle,
- William S. Bush,
- Akinori Miyashita,
- Goldie S. Byrd,
- Li-San Wang,
- Lindsay A. Farrer,
- Jonathan L. Haines,
- Richard Mayeux,
- Margaret A. Pericak-Vance,
- Gerard D. Schellenberg,
- Gyungah R. Jun,
- Christiane Reitz,
- Adam C. Naj,
- on behalf of Alzheimer’s Disease Genetics Consortium (ADGC)
Affiliations
- Farid Rajabli
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Penelope Benchek
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Giuseppe Tosto
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Nicholas Kushch
- The John P. Hussman Institute for Human Genomics, University of Miami
- Jin Sha
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania
- Katrina Bazemore
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania
- Congcong Zhu
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Wan-Ping Lee
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Jacob Haut
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania
- Kara L. Hamilton-Nelson
- The John P. Hussman Institute for Human Genomics, University of Miami
- Nicholas R. Wheeler
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Yi Zhao
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- John J. Farrell
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Michelle A. Grunin
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Yuk Yee Leung
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Pavel P. Kuksa
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Donghe Li
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Eder Lucio da Fonseca
- The John P. Hussman Institute for Human Genomics, University of Miami
- Jesse B. Mez
- Department of Neurology, Boston University Chobanian & Avedisian School of Medicine
- Ellen L. Palmer
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Jagan Pillai
- Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic
- Richard M. Sherva
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Yeunjoo E. Song
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Xiaoling Zhang
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Takeshi Ikeuchi
- Molecular Genetics Division, Brain Research Institute, Niigata University
- Taha Iqbal
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania
- Omkar Pathak
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Otto Valladares
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Dolly Reyes-Dumeyer
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Amanda B. Kuzma
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Erin Abner
- Sanders-Brown Center on Aging, Department of Epidemiology, College of Public Health, University of Kentucky
- Larry D. Adams
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Perrie M. Adams
- Department of Psychiatry, University of Texas Southwestern Medical Center
- Alyssa Aguirre
- Department of Neurology, Dell Medical School, University of Texas at Austin
- Marilyn S. Albert
- Department of Neurology, Johns Hopkins University
- Roger L. Albin
- Department of Neurology, University of Michigan
- Mariet Allen
- Department of Neuroscience, Mayo Clinic
- Lisa Alvarez
- Department of Pharmacology and Neuroscience, University of North Texas Health Science Center
- Liana G. Apostolova
- Departments of Neurology, Radiology, and Medical and Molecular Genetics, Indiana University School of Medicine
- Steven E. Arnold
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania
- Sanjay Asthana
- Geriatric Research, Education and Clinical Center (GRECC), University of Wisconsin
- Craig S. Atwood
- Geriatric Research, Education and Clinical Center (GRECC), University of Wisconsin
- Sanford Auerbach
- Department of Neurology, Boston University Chobanian & Avedisian School of Medicine
- Gayle Ayres
- Department of Neurology, Dell Medical School, University of Texas at Austin
- Clinton T. Baldwin
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Robert C. Barber
- Department of Pharmacology and Neuroscience, University of North Texas Health Science Center
- Lisa L. Barnes
- Department of Neurological Sciences, Rush University Medical Center
- Sandra Barral
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Thomas G. Beach
- Civin Laboratory for Neuropathology, Banner Sun Health Research Institute
- James T. Becker
- Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine
- Gary W. Beecham
- The John P. Hussman Institute for Human Genomics, University of Miami
- Duane Beekly
- National Alzheimer’s Coordinating Center, University of Washington
- Bruno A. Benitez
- Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine
- David Bennett
- Department of Neurological Sciences, Rush University Medical Center
- John Bertelson
- Department of Psychiatry , University of Texas at Austin/Dell Medical School
- Thomas D. Bird
- VA Puget Sound Health Care System/GRECC
- Deborah Blacker
- Department of Epidemiology, Harvard School of Public Health
- Bradley F. Boeve
- Department of Neurology, Mayo Clinic
- James D. Bowen
- Swedish Medical Center
- Adam Boxer
- Department of Neurology, University of California San Francisco
- James Brewer
- Department of Neurosciences, University of California San Diego
- James R. Burke
- Department of Medicine, Duke University
- Jeffrey M. Burns
- University of Kansas Alzheimer’s Disease Center, University of Kansas Medical Center
- Joseph D. Buxbaum
- Department of Genetics and Genomic Sciences, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai
- Nigel J. Cairns
- Department of Pathology and Immunology, Washington University
- Laura B. Cantwell
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Chuanhai Cao
- USF Health Byrd Alzheimer’s Institute, University of South Florida
- Christopher S. Carlson
- Fred Hutchinson Cancer Research Center
- Cynthia M. Carlsson
- Department of Medicine, University of Wisconsin
- Regina M. Carney
- Mental Health and Behavioral Science Service, Bruce W. Carter VA Medical Center
- Minerva M. Carrasquillo
- Department of Neuroscience, Mayo Clinic
- Scott Chasse
- Department of Genetics, University of North Carolina Chapel Hill
- Marie-Francoise Chesselet
- Neurogenetics Program, University of California Los Angeles
- Nathaniel A. Chin
- Geriatric Research, Education and Clinical Center (GRECC), University of Wisconsin
- Helena C. Chui
- University of California Los Angeles, University of Southern California
- Jaeyoon Chung
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Suzanne Craft
- Section of Gerontology and Geriatric Medicine Research, Wake Forest School of Medicine
- Paul K. Crane
- Department of Medicine, University of Washington
- David H. Cribbs
- Department of Neurology, University of California Irvine
- Elizabeth A. Crocco
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami
- Carlos Cruchaga
- NeuroGenomics and Informatics, Washington University
- Michael L. Cuccaro
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Munro Cullum
- Department of Psychiatry, University of Texas Southwestern Medical Center
- Eveleen Darby
- Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine
- Barbara Davis
- Department of Population and Data Sciences, University of Texas Southwestern Medical Center
- Philip L. De Jager
- Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center
- Charles DeCarli
- Department of Neurology, University of California Davis
- John DeToledo
- Departments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center
- Malcolm Dick
- Institute for Memory Impairments and Neurological Disorders, University of California Irvine
- Dennis W. Dickson
- Department of Neuroscience, Mayo Clinic
- Beth A. Dombroski
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Rachelle S. Doody
- Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine
- Ranjan Duara
- Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center
- NIlüfer Ertekin-Taner
- Department of Neuroscience, Mayo Clinic
- Denis A. Evans
- Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center
- Kelley M. Faber
- Department of Medical and Molecular Genetics, Indiana University
- Thomas J. Fairchild
- Office of Strategy and Measurement, University of North Texas Health Science Center
- Kenneth B. Fallon
- Department of Pathology, University of Alabama at Birmingham
- David W. Fardo
- Sanders-Brown Center on Aging, Department of Biostatistics, College of Public Health, University of Kentucky
- Martin R. Farlow
- Department of Neurology, Indiana University
- Victoria Fernandez-Hernandez
- Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine
- Steven Ferris
- Department of Psychiatry, New York University
- Robert P. Friedland
- Department of Neurology, University of Louisville School of Medicine
- Tatiana M. Foroud
- Department of Medical and Molecular Genetics, Indiana University
- Matthew P. Frosch
- C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital
- Brian Fulton-Howard
- Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai
- Douglas R. Galasko
- Department of Neurosciences, University of California San Diego
- Adriana Gamboa
- Department of Health Behavior and Health Systems, University of North Texas Health Science Center
- Marla Gearing
- Department of Pathology and Laboratory Medicine, Emory University
- Daniel H. Geschwind
- Neurogenetics Program, University of California Los Angeles
- Bernardino Ghetti
- Department of Pathology and Laboratory Medicine, Indiana University
- John R. Gilbert
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Rodney C.P. Go
- Department of Pathology, University of Alabama at Birmingham
- Alison M. Goate
- Department of Genetics and Genomic Sciences, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai
- Thomas J. Grabowski
- Department of Neurology, University of Washington
- Neill R. Graff-Radford
- Department of Neuroscience, Mayo Clinic
- Robert C. Green
- Division 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
- John H. Growdon
- Department of Neurology, Massachusetts General Hospital/Harvard Medical School
- Hakon Hakonarson
- Center for Applied Genomics, Children’s Hospital of Philadelphia
- James Hall
- Department of Pharmacology and Neuroscience, University of North Texas Health Science Center
- Ronald L. Hamilton
- Department of Pathology (Neuropathology), University of Pittsburgh
- Oscar Harari
- Department of Psychiatry, Washington University in St. Louis
- John Hardy
- UCL Institute of Neurology, University College London
- Lindy E. Harrell
- Department of Neurology, University of Alabama at Birmingham
- Elizabeth Head
- Department of Pathology and Laboratory Medicine, University of California Irvine
- Victor W. Henderson
- Department of Epidemiology and Population Health, Stanford University
- Michelle Hernandez
- Departments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center
- Timothy Hohman
- Vanderbilt Memory and Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center
- Lawrence S. Honig
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Ryan M. Huebinger
- Department of Surgery, University of Texas Southwestern Medical Center
- Matthew J. Huentelman
- Neurogenomics Division, Translational Genomics Research Institute
- Christine M. Hulette
- Department of Pathology, Duke University
- Bradley T. Hyman
- Department of Neurology, Massachusetts General Hospital/Harvard Medical School
- Linda S. Hynan
- Department of Psychiatry, University of Texas Southwestern Medical Center
- Laura Ibanez
- Department of Psychiatry, Washington University School of Medicine
- Gail P. Jarvik
- Department of Genome Sciences, University of Washington
- Suman Jayadev
- Department of Neurology, University of Washington
- Lee-Way Jin
- Department of Pathology and Laboratory Medicine, University of California Davis
- Kim Johnson
- Departments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center
- Leigh Johnson
- Department of Health Behavior and Health Systems, University of North Texas Health Science Center
- M. Ilyas Kamboh
- Department of Psychiatry, University of Pittsburgh
- Anna M. Karydas
- Department of Neurology, University of California San Francisco
- Mindy J. Katz
- Department of Neurology, Albert Einstein College of Medicine
- John S. Kauwe
- Department of Neuroscience, Brigham Young University
- Jeffrey A. Kaye
- Department of Neurology, Oregon Health and Science University
- C. Dirk Keene
- Department of Laboratory Medicine and Pathology, University of Washington
- Aisha Khaleeq
- Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine
- Masataka Kikuchi
- Molecular Genetics Division, Brain Research Institute, Niigata University
- Ronald Kim
- Department of Pathology and Laboratory Medicine, University of California Irvine
- Janice Knebl
- Department of Health Behavior and Health Systems, University of North Texas Health Science Center
- Neil W. Kowall
- Department of Neurology, Boston University Chobanian & Avedisian School of Medicine
- Joel H. Kramer
- Department of Neuropsychology, University of California San Francisco
- Walter A. Kukull
- Department of Epidemiology, University of Washington
- Frank M. LaFerla
- Department of Neurobiology and Behavior, University of California Irvine
- James J. Lah
- Department of Neurology, Emory University
- Eric B. Larson
- National Center for PTSD, Boston VA Healthcare System
- Alan Lerner
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- James B. Leverenz
- Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic
- Allan I. Levey
- Department of Neurology, Emory University
- Andrew P. Lieberman
- Department of Pathology, University of Michigan
- Richard B. Lipton
- Department of Neurology, Albert Einstein College of Medicine
- Mark Logue
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Oscar L. Lopez
- Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine
- Kathryn L. Lunetta
- Department of Biostatistics, Boston University School of Public Health
- Constantine G. Lyketsos
- Department of Psychiatry, Johns Hopkins University
- Douglas Mains
- Department of Health Behavior and Health Systems, University of North Texas Health Science Center
- Flanagan E. Margaret
- Department of Pathology, Northwestern University Feinberg School of Medicine
- Daniel C. Marson
- Department of Neurology, University of Alabama at Birmingham
- Eden RR. Martin
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Frank Martiniuk
- Department of Medicine - Pulmonary, New York University
- Deborah C. Mash
- Department of Neurology, Miller School of Medicine, University of Miami
- Eliezer Masliah
- Department of Neurosciences, University of California San Diego
- Paul Massman
- Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine
- Arjun Masurkar
- Department of Psychiatry, New York University
- Wayne C. McCormick
- Department of Medicine, University of Washington
- Susan M. McCurry
- School of Nursing Northwest Research Group on Aging, University of Washington
- Andrew N. McDavid
- Fred Hutchinson Cancer Research Center
- Stefan McDonough
- Pfizer Worldwide Research and Development
- Ann C. McKee
- Department of Neurology, Boston University Chobanian & Avedisian School of Medicine
- Marsel Mesulam
- Department of Pathology, Northwestern University Feinberg School of Medicine
- Bruce L. Miller
- Weill Institute for Neurosciences, Memory and Aging Center, University of California San Francisco
- Carol A. Miller
- Department of Pathology, University of Southern California
- Joshua W. Miller
- Department of Pathology and Laboratory Medicine, University of California Davis
- Thomas J. Montine
- Department of Pathology, Stanford University School of Medicine
- Edwin S. Monuki
- Department of Pathology and Laboratory Medicine and Alzheimer’s Disease Research Center, University of California Irvine
- John C. Morris
- Department of Pathology and Immunology, Washington University
- Shubhabrata Mukherjee
- Department of Medicine, University of Washington
- Amanda J. Myers
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami
- Trung Nguyen
- Department of Neurology, University of Texas Southwestern Medical Center
- Thomas Obisesan
- Department of Research Regulatory Compliance, College of Medicine, Howard Unviersity
- Sid O’Bryant
- Institute for Translational Research, University of North Texas Health Science Center
- John M. Olichney
- Center for Mind and Brain and Department of Neurology, University of California Davis
- Marcia Ory
- Center for Population Health and Aging, Texas AandM University Health Science Center
- Raymond Palmer
- Department of Family and Community Medicine, University of Texas Health Science Center San Antonio
- Joseph E. Parisi
- Department of Laboratory Medicine and Pathology, Mayo Clinic
- Henry L. Paulson
- Department of Neurology, University of Michigan
- Valory Pavlik
- Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine
- David Paydarfar
- Department of Neurology, Dell Medical School, University of Texas at Austin
- Victoria Perez
- Departments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center
- Elaine Peskind
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine
- Ronald C. Petersen
- Department of Neurology, Mayo Clinic
- Helen Petrovitch
- Pacific Health Research & Education Institute, VA Pacific Islands Healthcare System
- Aimee Pierce
- Department of Neurology, University of California Irvine
- Marsha Polk
- Department of Family and Community Medicine, University of Texas Health Science Center San Antonio
- Wayne W. Poon
- Institute for Memory Impairments and Neurological Disorders, University of California Irvine
- Huntington Potter
- Department of Neurology, University of Colorado School of Medicine
- Liming Qu
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Mary Quiceno
- Department of Internal Medicine and Geriatrics, University of North Texas Health Science Center
- Joseph F. Quinn
- Department of Neurology, Oregon Health and Science University
- Ashok Raj
- USF Health Byrd Alzheimer’s Institute, University of South Florida
- Murray Raskind
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine
- Eric M. Reiman
- Neurogenomics Division, Translational Genomics Research Institute
- Barry Reisberg
- Department of Psychiatry, New York University
- Joan S. Reisch
- Department of Population and Data Sciences, University of Texas Southwestern Medical Center
- John M. Ringman
- Department of Neurology, University of California Los Angeles
- Erik D. Roberson
- Department of Neurology, University of Alabama at Birmingham
- Monica Rodriguear
- Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine
- Ekaterina Rogaeva
- Tanz Centre for Research in Neurodegenerative Disease, University of Toronto
- Howard J. Rosen
- Department of Neurology, University of California San Francisco
- Roger N. Rosenberg
- Department of Neurology, University of Texas Southwestern Medical Center
- Donald R. Royall
- Departments 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,
- Marwan Sabbagh
- Department of Neurology, Barrow Neurological Institute St. Joseph’s Hospital and Medical Center
- A. Dessa Sadovnick
- Department of Medical Genetics, University of British Columbia
- Mark A. Sager
- Department of Medicine, University of Wisconsin
- Mary Sano
- Department of Psychiatry, Mount Sinai School of Medicine
- Andrew J. Saykin
- Department of Medical and Molecular Genetics, Indiana University
- Julie A. Schneider
- Department of Neurological Sciences, Rush University Medical Center
- Lon S. Schneider
- University of California Los Angeles, University of Southern California
- William W. Seeley
- Department of Neurology, University of California San Francisco
- Susan H. Slifer
- The John P. Hussman Institute for Human Genomics, University of Miami
- Scott Small
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Amanda G. Smith
- USF Health Byrd Alzheimer’s Institute, University of South Florida
- Janet P. Smith
- Department of Population and Data Sciences, University of Texas Southwestern Medical Center
- Joshua A. Sonnen
- Department of Laboratory Medicine and Pathology, University of Washington
- Salvatore Spina
- Department of Pathology and Laboratory Medicine, Indiana University
- Peter St George-Hyslop
- Cambridge Institute for Medical Research, University of Cambridge
- Takiyah D. Starks
- Maya Angelou Center for Health Equity, Wake Forest School of Medicine
- Robert A. Stern
- Department of Neurology, Boston University Chobanian & Avedisian School of Medicine
- Alan B. Stevens
- Center for Applied Health Research, Baylor Scott & White Health
- Stephen M. Strittmatter
- Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine
- David Sultzer
- Department of Psychiatry and Human Behavior, University of California Irvine
- Russell H. Swerdlow
- University of Kansas Alzheimer’s Disease Center, University of Kansas Medical Center
- Rudolph E. Tanzi
- Department of Neurology, Massachusetts General Hospital/Harvard Medical School
- Jeffrey L. Tilson
- Renaissance Computing Institute, University of North Carolina Chapel Hill
- John Q. Trojanowski
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Juan C. Troncoso
- Department of Pathology, Johns Hopkins University
- Magda Tsolaki
- Department of Neurology, Aristotle University of Thessaloniki
- Debby W. Tsuang
- VA Puget Sound Health Care System/GRECC
- Vivianna M. Van Deerlin
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Linda J. van Eldik
- Sanders-Brown Center on Aging, Department of Neuroscience, College of Medicine, University of Kentucky
- Jeffery M. Vance
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Badri N. Vardarajan
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Robert Vassar
- Department of Pathology, Northwestern University Feinberg School of Medicine
- Harry V. Vinters
- Department of Neurology, University of California Los Angeles
- Jean-Paul Vonsattel
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Sandra Weintraub
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine
- Kathleen A. Welsh-Bohmer
- Department of Medicine, Duke University
- Patrice L. Whitehead
- The John P. Hussman Institute for Human Genomics, University of Miami
- Ellen M. Wijsman
- Department of Genome Sciences, University of Washington
- Kirk C. Wilhelmsen
- Department of Genetics, University of North Carolina Chapel Hill
- Benjamin Williams
- Department of Pathology, Oregon Health and Science University
- Jennifer Williamson
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Henrik Wilms
- Departments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center
- Thomas S. Wingo
- Department of Neurology, Emory University
- Thomas Wisniewski
- Department of Psychiatry, New York University Grossman School of Medicine
- Randall L. Woltjer
- Department of Pathology, Oregon Health and Science University
- Martin Woon
- Department of Psychiatry , University of Texas at Austin/Dell Medical School
- Clinton B. Wright
- Evelyn F. McKnight Brain Institute, Department of Neurology, Miller School of Medicine, University of Miami
- Chuang-Kuo Wu
- Departments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center
- Steven G. Younkin
- Department of Neuroscience, Mayo Clinic
- Chang-En Yu
- Department of Medicine, University of Washington
- Lei Yu
- Wisconsin Alzheimer’s Disease Research Center
- Xiongwei Zhu
- Social Sciences & Health Policy, Wake Forest School of Medicine
- Brian W. Kunkle
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- William S. Bush
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Akinori Miyashita
- Molecular Genetics Division, Brain Research Institute, Niigata University
- Goldie S. Byrd
- Department of Ophthalmology, Boston University Chobanian & Avedisian School of Medicine
- Li-San Wang
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Lindsay A. Farrer
- Department of Neurology, Boston University Chobanian & Avedisian School of Medicine
- Jonathan L. Haines
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Richard Mayeux
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University
- Margaret A. Pericak-Vance
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Gerard D. Schellenberg
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Gyungah R. Jun
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Christiane Reitz
- Department of Neurology, Columbia University
- Adam C. Naj
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania
- on behalf of Alzheimer’s Disease Genetics Consortium (ADGC)
- DOI
- https://doi.org/10.1186/s13059-025-03564-z
- Journal volume & issue
-
Vol. 26,
no. 1
pp. 1 – 34
Abstract
Abstract Background Limited 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. Results We 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). Conclusions Using 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.
Keywords
- Genome-wide association study (GWAS)
- GWAS meta-analysis,
- Alzheimer disease
- Multi-ancestry
- Population-specific
