Evidence map›Paper›PMID 25199842›Full record

SynthesisJAMA neurology2014

Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.

Adam C Naj, Gyungah Jun, Christiane Reitz, Brian W Kunkle, William Perry, Yo Son Park, Gary W Beecham, Ruchita A Rajbhandary, Kara L Hamilton-Nelson, Li-San Wang and 165 more

Erratum issuedOpen access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in JAMA neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 119 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 8 pooled it
16.1field-weighted citation impact, top 1% of its field
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

119 citing papers in PubMed, 8 syntheses or guidelines pooled it, 194 citations in OpenAlex.

  1. A haptoglobin (HP) structural variant alters the effect of APOE alleles on Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Genetic association of CALHM1 rs2986017 polymorphism with risk of Alzheimer's disease: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2016
    Pooled it
  8. Pooled it
  9. Article
  10. Article
  11. Article
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  14. Ms4a4a deficiency ameliorates plaque pathology in a mouse model of amyloid accumulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Alzheimer's Disease Neuropathological Change in Aged Non-Primate Mammals.International journal of molecular sciences · 2024
    Review

59 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

175 authors at 20 institutions in 4 countries.

Adam C NajDepartment of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Gyungah JunGenetics Program, Department of Medicine, Boston University, Boston, Massachusetts4Department of Biostatistics, Boston University, Boston, Massachusetts5Department of Ophthalmology, Boston University, Boston, Massachusetts.
Christiane ReitzTaub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York7Gertrude H. Sergievsky Center, Columbia University, New York, New York8Department of Neurology, Columbia University, New York, New.
Brian W KunkleJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
William PerryJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
Yo Son ParkThe Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida.
Gary W BeechamJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida9The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida.
Ruchita A RajbhandaryJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
Kara L Hamilton-NelsonJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
Li-San WangDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
John S K KauweDepartment of Biology, Brigham Young University, Provo, Utah.
Matthew J HuentelmanNeurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona.
Amanda J MyersDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida.
Thomas D BirdDepartment of Neurology, University of Washington, Seattle15Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, Minnesota.
Clinton T BaldwinGenetics Program, Department of Medicine, Boston University, Boston, Massachusetts.
Gail P JarvikDepartment of Genome Sciences, University of Washington, Seattle18Division of Medical Genetics, Department of Medicine, University of Washington, Seattle.
Paul K CraneDepartment of Medicine, University of Washington, Seattle.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.
M Michael BarmadaDepartment of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
F Yesim DemirciDepartment of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
Carlos CruchagaDepartment of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, School of Medicine, Washington University in St Louis, St Louis, Missouri.
Patricia L KramerDepartment of Neurology, Oregon Health & Science University, Portland24Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland.
Nilufer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida26Department of Neurology, Mayo Clinic, Jacksonville, Florida.
John HardyInstitute of Neurology, University College London, London, England.
Neill R Graff-RadfordDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida26Department of Neurology, Mayo Clinic, Jacksonville, Florida.
Robert C GreenDivision of Genetics, Department of Medicine, and Partners Center for Personalized Genetic Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Eric B LarsonDepartment of Medicine, University of Washington, Seattle29Group Health Research Institute, Group Health Cooperative, Seattle, Washington.
Peter H St George-HyslopTanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada30Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
Joseph D BuxbaumDepartment of Neuroscience, Mount Sinai School of Medicine, New York, New York32Department of Psychiatry, Mount Sinai School of Medicine, New York, New York33Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.
Denis A EvansRush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois.
Julie A SchneiderDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois36Neuropathology, Department of Pathology, Rush University Medical Center, Chicago, Illinois.
Kathryn L LunettaDepartment of Biostatistics, Boston University, Boston, Massachusetts.
M Ilyas KambohDepartment of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania37Alheimer Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
Andrew J SaykinDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis39Department of Radiology and Imaging Sciences, Indiana University, Indianapolis.
Eric M ReimanNeurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona40Arizona Alzheimer's Consortium, Phoenix41Department of Psychiatry, University of Arizona, Phoenix42Banner Alzheimer's Institute, Phoenix, Arizona.
Philip L De JagerProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology and Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts44Program in Medical and Population Genetics, Broad Ins.
David A BennettDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois45Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
John C MorrisDepartment of Pathology and Immunology, Washington University in St Louis, St Louis, Missouri47Department of Neurology, Washington University in St Louis, St Louis, Missouri.
Thomas J MontineDepartment of Pathology, University of Washington, Seattle.
Alison M GoateDepartment of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, School of Medicine, Washington University in St Louis, St Louis, Missouri.
Deborah BlackerDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts50Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston.
Debby W TsuangGeriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington51Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
Hakon HakonarsonCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Walter A KukullDepartment of Epidemiology, University of Washington, Seattle.
Tatiana M ForoudDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis.
Eden R MartinJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida9The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida.
Jonathan L HainesDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee55Vanderbilit Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee.
Richard P MayeuxTaub Institute on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York57Gertrude H. Sergievsky Center, Columbia University, New York, New York58Department of Neurology, Columbia University, New York, New York.
Lindsay A FarrerGenetics Program, Department of Medicine, Boston University, Boston, Massachusetts4Department of Biostatistics, Boston University, Boston, Massachusetts5Department of Ophthalmology, Boston University, Boston, Massachusetts59Department of Epidemiology, Bos.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida9The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida.
Alzheimer Disease Genetics Consortium
Marilyn S AlbertDepartment of Neurology, Johns Hopkins University, Baltimore, Maryland.
Roger L AlbinDepartment of Neurology, University of Michigan, Ann Arbor63Geriatric Research, Education and Clinical Center (GRECC), VA Ann Arbor Healthcare System (VAAAHS), Ann Arbor, Michigan64Michigan Alzheimer Disease Center, Ann Arbor.
Liana G ApostolovaDepartment of Neurology, University of California Los Angeles, Los Angeles.
Steven E ArnoldDepartment of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Robert BarberDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth.
Lisa L BarnesDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois68Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois.
Thomas G BeachCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Phoenix, Arizona.
James T BeckerDepartments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Duane BeeklyNational Alzheimer's Coordinating Center, University of Washington, Seattle.
Eileen H BigioDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois73Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, Illinois.
James D BowenSwedish Medical Center, Seattle, Washington.
Adam BoxerDepartment of Neurology, University of California San Francisco, San Francisco.
James R BurkeDepartment of Medicine, Duke University, Durham, North Carolina.
Nigel J CairnsDepartment of Pathology and Immunology, Washington University in St Louis, St Louis, Missouri.
Laura B CantwellDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Chuanhai CaoUSF Health Byrd Alzheimer's Institute, University of South Florida, Tampa.
Chris S CarlsonFred Hutchinson Cancer Research Center, Seattle, Washington.
Regina M CarneyDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida.
Minerva M CarrasquilloDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida.
Steven L CarrollDepartment of Pathology, University of Alabama at Birmingham, Birmingham.
Helena C ChuiDepartment of Neurology, University of Southern California, Los Angeles.
David G ClarkDepartment of Neurology, University of Alabama at Birmingham, Birmingham.
Jason CorneveauxNeurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona.
David H CribbsDepartment of Neurology, University of California Irvine, Irvine.
Elizabeth A CroccoDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida.
Charles DeCarliDepartment of Neurology, University of California Davis, Sacramento.
Steven T DeKoskyUniversity of Virginia School of Medicine, Charlottesville.
Malcolm DickInstitute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida.
Ranjan DuaraWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida.
Kelley M FaberDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis.
Kenneth B FallonDepartment of Pathology, University of Alabama at Birmingham, Birmingham.
Martin R FarlowDepartment of Neurology, Indiana University, Indianapolis.
Steven FerrisDepartment of Psychiatry, New York University, New York.
Matthew P FroschC.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown.
Douglas R GalaskoDepartment of Neurosciences, University of California San Diego, La Jolla.
Mary GanguliDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Marla GearingDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia93Emory Alzheimer's Disease Center, Emory University, Atlanta, Georgia.
Daniel H GeschwindNeurogenetics Program, University of California Los Angeles, Los Angeles.
Bernardino GhettiDepartment of Pathology and Laboratory Medicine, Indiana University, Indianapolis.
John R GilbertJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida9The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida.
Jonathan D GlassDepartment of Neurology, Emory University, Atlanta, Georgia.
John H GrowdonDepartment of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston.
Ronald L HamiltonDepartment of Pathology (Neuropathology), University of Pittsburgh, Pittsburgh, Pennsylvania.
Lindy E HarrellDepartment of Neurology, University of Alabama at Birmingham, Birmingham.
Elizabeth HeadSanders-Brown Center on Aging, Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington.
Lawrence S HonigTaub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York.
Christine M HuletteDepartment of Pathology, Duke University, Durham, North Carolina.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston.
Gregory A JichaSanders-Brown Center on Aging, Department Neurology, University of Kentucky, Lexington.
Lee-Way JinDepartment of Pathology and Laboratory Medicine, University of California Davis, Sacramento.
Anna KarydasDepartment of Neurology, University of California San Francisco, San Francisco.
Jeffrey A KayeDepartment of Neurology, Oregon Health & Science University, Portland103Department of Neurology, Portland Veterans Affairs Medical Center, Portland, Oregon.
Ronald KimDepartment of Pathology and Laboratory Medicine, University of California Irvine, Irvine.
Edward H KooDepartment of Neurosciences, University of California San Diego, La Jolla.
Neil W KowallDepartment of Neurology, Boston University, Boston, Massachusetts105Department of Pathology, Boston University, Boston, Massachusetts.
Joel H KramerDepartment of Neuropsychology, University of California San Francisco, San Francisco.
Frank M LaFerlaDepartment of Neurobiology and Behavior, University of California Irvine, Irvine.
James J LahDepartment of Neurology, Emory University, Atlanta, Georgia.
James B LeverenzDepartment of Pathology, University of Washington, Seattle.
Allan I LeveyDepartment of Neurology, Emory University, Atlanta, Georgia.
Ge LiDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
Andrew P LiebermanDepartment of Pathology, University of Michigan, Ann Arbor.
Chiao-Feng LinDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Oscar L LopezAlheimer Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
Constantine G LyketsosDepartment of Psychiatry, Johns Hopkins University, Baltimore, Maryland.
Wendy J MackDepartment of Preventive Medicine, University of Southern California, Los Angeles.
Frank MartiniukDepartment of Medicine - Pulmonary, New York University, New York.
Deborah C MashDepartment of Neurology, University of Miami, Miami, Florida.
Eliezer MasliahDepartment of Neurosciences, University of California San Diego, La Jolla113Department of Pathology, University of California San Diego, La Jolla.
Wayne C McCormickDepartment of Medicine, University of Washington, Seattle.
Susan M McCurrySchool of Nursing Northwest Research Group on Aging, University of Washington, Seattle.
Andrew N McDavidFred Hutchinson Cancer Research Center, Seattle, Washington.
Ann C McKeeDepartment of Neurology, Boston University, Boston, Massachusetts105Department of Pathology, Boston University, Boston, Massachusetts.
Marsel MesulamCognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, Illinois115Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Bruce L MillerDepartment of Neurology, University of California San Francisco, San Francisco.
Carol A MillerDepartment of Pathology, University of Southern California, Los Angeles.
Joshua W MillerDepartment of Pathology and Laboratory Medicine, University of California Davis, Sacramento.
Jill R MurrellDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis95Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis.
John M OlichneyDepartment of Neurology, University of California Davis, Sacramento.
Vernon S PankratzDepartment of Biostatistics, Mayo Clinic, Rochester, Minnesota.
Joseph E ParisiDepartment of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota119Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Henry L PaulsonDepartment of Neurology, University of Michigan, Ann Arbor.
Elaine PeskindDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, Minnesota.
Aimee PierceDepartment of Neurology, University of California Irvine, Irvine.
Wayne W PoonInstitute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine.
Huntington PotterUSF Health Byrd Alzheimer's Institute, University of South Florida, Tampa.
Joseph F QuinnDepartment of Neurology, Oregon Health & Science University, Portland.
Ashok RajUSF Health Byrd Alzheimer's Institute, University of South Florida, Tampa.
Murray RaskindDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
Barry ReisbergDepartment of Psychiatry, New York University, New York120Alzheimer's Disease Center, New York University, New York.
John M RingmanDepartment of Neurology, University of California Los Angeles, Los Angeles.
Erik D RobersonDepartment of Neurology, University of Alabama at Birmingham, Birmingham.
Howard J RosenDepartment of Neurology, University of California San Francisco, San Francisco.
Roger N RosenbergDepartment of Neurology, University of Texas Southwestern, Dallas.
Mary SanoDepartment of Psychiatry, Mount Sinai School of Medicine, New York, New York.
Lon S SchneiderDepartment of Neurology, University of Southern California, Los Angeles122Department of Psychiatry, University of Southern California, Los Angeles.
William W SeeleyDepartment of Neurology, University of California San Francisco, San Francisco.
Amanda G SmithUSF Health Byrd Alzheimer's Institute, University of South Florida, Tampa.
Joshua A SonnenDepartment of Pathology, University of Washington, Seattle.
Salvatore SpinaDepartment of Pathology and Laboratory Medicine, Indiana University, Indianapolis.
Robert A SternDepartment of Neurology, Boston University, Boston, Massachusetts.
Rudolph E TanziDepartment of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston.
Tricia A Thornton-WellsVanderbilit Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee.
John Q TrojanowskiDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Juan C TroncosoDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland.
Otto ValladaresDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Vivianna M Van DeerlinDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Linda J Van EldikSanders-Brown Center on Aging, Department of Anatomy and Neurobiology, University of Kentucky, Lexington.
Badri N VardarajanDepartment of Neurology, Columbia University, New York, New York.
Harry V VintersDepartment of Neurology, University of California Los Angeles, Los Angeles125Department of Pathology & Laboratory Medicine, University of California Los Angeles, Los Angeles.
Jean Paul VonsattelTaub Institute on Alzheimer's Disease and the Aging Brain, Department of Pathology, Columbia University, New York, New York.
Sandra WeintraubCognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, Illinois127Department of Psychiatry, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Kathleen A Welsh-BohmerDepartment of Medicine, Duke University, Durham, North Carolina128Department of Psychiatry & Behavioral Sciences, Duke University, Durham, North Carolina.
Jennifer WilliamsonTaub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York.
Sarah WishnekJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
Randall L WoltjerDepartment of Pathology, Oregon Health & Science University, Portland.
Clinton B WrightEvelyn F. McKnight Brain Institute, Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida.
Steven G YounkinDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida.
Chang-En YuDepartment of Medicine, University of Washington, Seattle.
Lei YuDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
University of Washington · USUniversity of Miami · USUniversity of Pennsylvania · USBoston University · USUniversity of California, San Francisco · USUniversity of Pittsburgh · USColumbia University · USIndiana University – Purdue University Indianapolis · USRush University Medical Center · USUniversity of California, Davis · USDr. John T. Macdonald Foundation · USDuke University · USEmory University · USOregon Health & Science University · USTranslational Genomics Research Institute · USUniversity of Alabama at Birmingham · USUniversity of California, Irvine · USUniversity of California, Los Angeles · USUniversity of Southern California · USWashington University in St. Louis · US

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI Laurel A Beckett · 2016 to 2026
$226.7M
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
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 · 1985 to 2026
$69.5M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 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 BREWER, JAMES B · 1985 to 2018
$55.4M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI FAGAN, ANNE · 1985 to 2019
$52.1M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
CIHRHoward Hughes Medical InstituteMedical Research CouncilNCATS NIH HHS UL1 TR000135NCATS NIH HHS UL1 TR001108NCI NIH HHS R01 CA129769NCI NIH HHS U54 CA132378NCI NIH HHS U54 CA137788NCRR NIH HHS M01 RR000096NCRR NIH HHS MO1RR00096NCRR NIH HHS UL1RR02777NCRR NIH HHS UL1 RR029893NHGRI NIH HHS HG004610NHGRI NIH HHS U01 HG004610NIA NIH HHS 1R01AG035137NIA NIH HHS 1RC2AG036502NIA NIH HHS 5R01AG012101NIA NIH HHS 5R01AG013616NIA NIH HHS 5R01AG022374NIA NIH HHS AG010491NIA NIH HHS AG019757NIA NIH HHS AG021547NIA NIH HHS AG025688NIA NIH HHS AG027944NIA NIH HHS AG030653NIA NIH HHS AG034504NIA NIH HHS AG041718NIA NIH HHS AG05128NIA NIH HHS K01 AG030514NIA NIH HHS P01 AG002219NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG010491NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG03991NIA 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 AG062421NIA NIH HHS P30 AG08051NIA NIH HHS P30AG10133NIA NIH HHS P50 AG005128NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA 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 AG008702NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG016575NIA NIH HHS P50 AG016576NIA NIH HHS P50 AG016577NIA NIH HHS P50 AG016582NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA 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 AG019757NIA NIH HHS R01 AG020688NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG022374NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG026390NIA NIH HHS R01 AG026916NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG031581NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG034504NIA NIH HHS R01 AG035137NIA NIH HHS R01 AG041232NIA NIH HHS R01 AG041718NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG15819NIA NIH HHS R01 AG17917NIA NIH HHS R01 AG30146NIA NIH HHS R01AG33193NIA NIH HHS R37 AG015473NIA NIH HHS RC2 AG036502NIA NIH HHS RC2 AG036528NIA NIH HHS RC2 AG036535NIA NIH HHS RF1 AG015819NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG10483NIA NIH HHS U19 AG024904NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG026390NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG056270NIA NIH HHS UO1 AG06781NIEHS NIH HHS P30 ES013508NIMH NIH HHS MH60451NIMH NIH HHS P50 MH060451NIMH NIH HHS R01 MH080295NINDS NIH HHS NS39764NINDS NIH HHS P50 NS039764NINDS NIH HHS R01 NS059873NINDS NIH HHS R01 NS080820Parkinson's UK G-0907Wellcome Trust 081864Wellcome Trust 089703Wellcome Trust 100140
6 · The paper itself

Abstract

importanceBecause APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants.

objectivesTo investigate the effects of known Alzheimer disease risk loci in modifying AAO and to estimate their cumulative effect on AAO variation using data from genome-wide association studies in the Alzheimer Disease Genetics Consortium. DESIGN, SETTING, AND

participantsThe Alzheimer Disease Genetics Consortium comprises 14 case-control, prospective, and family-based data sets with data on 9162 participants of white race/ethnicity with Alzheimer disease occurring after age 60 years who also had complete AAO information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single-nucleotide polymorphisms most significantly associated with risk at 10 confirmed LOAD loci were examined in linear modeling of AAO, and individual data set results were combined using a random-effects, inverse variance-weighted meta-analysis approach to determine whether they contribute to variation in AAO. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. MAIN OUTCOMES AND MEASURES: Age at disease onset abstracted from medical records among participants with LOAD diagnosed per standard criteria.

resultsAnalysis confirmed the association of APOE with earlier AAO (P = 3.3 × 10(-96)), with associations in CR1 (rs6701713, P = 7.2 × 10(-4)), BIN1 (rs7561528, P = 4.8 × 10(-4)), and PICALM (rs561655, P = 2.2 × 10(-3)) reaching statistical significance (P < .005). Risk alleles individually reduced AAO by 3 to 6 months. Burden analyses demonstrated that APOE contributes to 3.7% of the variation in AAO (R(2) = 0.256) over baseline (R(2) = 0.221), whereas the other 9 loci together contribute to 2.2% of the variation (R(2) = 0.242). CONCLUSIONS AND RELEVANCE: We confirmed an association of APOE (OMIM 107741) variants with AAO among affected participants with LOAD and observed novel associations of CR1 (OMIM 120620), BIN1 (OMIM 601248), and PICALM (OMIM 603025) with AAO. In contrast to earlier hypothetical modeling, we show that the combined effects of Alzheimer disease risk variants on AAO are on the scale of, but do not exceed, the APOE effect. While the aggregate effects of risk loci on AAO may be significant, additional genetic contributions to AAO are individually likely to be small.

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudyAdultAgedAged, 80 and overAge of OnsetAlzheimer DiseaseFemaleGenetic LociGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideProspective StudiesRisk Factors

Identifiers

PMID25199842
PMCPMC4314944
OpenAlexW2029563076

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