Evidence map›Paper›PMID 26365416›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2016

Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease.

Brian W Kunkle, James Jaworski, Sandra Barral, Badri Vardarajan, Gary W Beecham, Eden R Martin, Laura S Cantwell, Amanda Partch, Thomas D Bird, Wendy H Raskind and 11 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Ancestral genomic functional differences in oligodendroglia: implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Alzheimer's Disease: An Updated Overview of Its Genetics.International journal of molecular sciences · 2023
    Review
  8. Genetic architecture of Alzheimer's disease.Neurobiology of disease · 2020
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Genomic variants, genes, and pathways of Alzheimer's disease: An overview.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017
    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

21 authors at 9 institutions in 1 country.

Brian W KunkleJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
James JaworskiJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Sandra BarralThe Taub Institute of Research on Alzheimer's Disease, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Badri VardarajanThe Taub Institute of Research on Alzheimer's Disease, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Gary W BeechamJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Eden R MartinJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Laura S CantwellDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Amanda PartchDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Thomas D BirdDepartment of Neurology, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
Wendy H RaskindDepartment of Medicine, University of Washington, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Anita L DeStefanoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Regina M CarneyJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
Michael CuccaroJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Jeffrey M VanceJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Lindsay A FarrerDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA; Department of Medicine (Biomedical Genetics), Boston University School of Medicine and Public Health, MA, USA; Department of Neurology, Boston University School of Medicine and Public Health, MA, USA; Department of Ophthalmology, Boston University School of Medicine and Public Health, MA, USA; Department of Epidemiology, Boston University School of Public Health, MA, USA.
Alison M GoateDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Richard P MayeuxThe Taub Institute of Research on Alzheimer's Disease, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jonathan L HainesDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA. Electronic address: mpericak@med.miami.edu.
Dr. John T. Macdonald Foundation · USUniversity of Miami · USUniversity of Pennsylvania · USBoston University · USColumbia University · USUniversity of Washington · USWashington University in St. Louis · USCase Western Reserve University · USIndiana University – Purdue University Indianapolis · US

Funding

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
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
The National Institute on Aging (NIA) Late Onset of Alzheimer's Disease (LOAD) Family-Based Study (FBS)U24AG056270 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gary Wayne Beecham, TATIANA M. FOROUD · 2017 to 2026
$31.4M
Neuropathology CoreP30AG013846 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOWALL, NEIL W. · 1996 to 2020
$29.1M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Consortium for Alzheimers Sequence Analysis (CASA)UF1AG047133 · NIA · UNIVERSITY OF PENNSYLVANIA · PI FARRER, LINDSAY A., HAINES, JONATHAN L · 2014 to 2014
$12.6M
Genetic Studies of Dementia in the AmishR01AG019085 · NIA · VANDERBILT UNIVERSITY · PI HAINES, JONATHAN L · 2001 to 2011
$11.0M
Genetic Epidemiology of Alzheimer's Disease in HispanicsR37AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2004 to 2013
$10.8M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Genetic Epidemiology of Alzheimer's Disease in African AmericansR01AG028786 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MANLY, JENNIFER JAIE · 2007 to 2011
$7.3M
NCATS NIH HHS UL1 TR001108NHLBI NIH HHS R01 HL105756NIA NIH HHS 5P50-AG008702-25NIA NIH HHS L30 AG032934NIA NIH HHS P30 AG013846NIA NIH HHS P30-AG13846NIA NIH HHS P50 AG008702NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG025259NIA NIH HHS R01-AG025259NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG028786NIA NIH HHS R01 AG028786-02NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG041797NIA NIH HHS R37 AG015473NIA NIH HHS R37AG015473NIA NIH HHS RC2 AG036528NIA NIH HHS RC2AG036528NIA NIH HHS U01 AG016976NIA NIH HHS U01AG032934NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG056270NIA NIH HHS UF1 AG047133NINDS NIH HHS 1R01 NS069719-01NINDS NIH HHS R01 NS069719Wellcome Trust
6 · The paper itself

Abstract

introductionFew high penetrance variants that explain risk in late-onset Alzheimer's disease (LOAD) families have been found.

methodsWe performed genome-wide linkage and identity-by-descent (IBD) analyses on 41 non-Hispanic white families exhibiting likely dominant inheritance of LOAD, and having no mutations at known familial Alzheimer's disease (AD) loci, and a low burden of APOE ε4 alleles.

resultsTwo-point parametric linkage analysis identified 14 significantly linked regions, including three novel linkage regions for LOAD (5q32, 11q12.2-11q14.1, and 14q13.3), one of which replicates a genome-wide association LOAD locus, the MS4A6A-MS4A4E gene cluster at 11q12.2. Five of the 14 regions (3q25.31, 4q34.1, 8q22.3, 11q12.2-14.1, and 19q13.41) are supported by strong multipoint results (logarithm of odds [LOD*] ≥1.5). Nonparametric multipoint analyses produced an additional significant locus at 14q32.2 (LOD* = 4.18). The 1-LOD confidence interval for this region contains one gene, C14orf177, and the microRNA Mir_320, whereas IBD analyses implicates an additional gene BCL11B, a regulator of brain-derived neurotrophic signaling, a pathway associated with pathogenesis of several neurodegenerative diseases. DISCUSSION: Examination of these regions after whole-genome sequencing may identify highly penetrant variants for familial LOAD.

Indexed as

Genetic LinkageGenome-Wide Association StudyAgedAged, 80 and overAlzheimer DiseaseApolipoproteins EGenetic Predisposition to DiseaseHumansMiddle AgedPedigreeWhite PeopleApolipoproteins EFamilialGeneticsHigh penetranceIdentity by descentLate-onset Alzheimer's diseaseLinkageNon-Hispanic white

Identifiers

PMID26365416
PMCPMC4717829
OpenAlexW1632374221

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.