SynthesisNeurology2014
The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 4 pooled it
4.2field-weighted citation impact, top 7% of its field
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.
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.
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Who cites it
24 citing papers in PubMed, 4 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017Pooled it
- The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Pooled it
- TREM2 variants and 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 · 2015Pooled it
- Lack of genetic association between TREM2 and Alzheimer's disease in East Asian population: a systematic review and meta-analysis.American journal of Alzheimer's disease and other dementias · 2015Pooled it
- TREM2 and microglial immunity in Alzheimer's disease: mechanisms, genetics, and therapeutic opportunities.Frontiers in immunology · 2026Review
- TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies.Molecular neurodegeneration · 2025Review
- Biophysical characterization of TREM2 missense variants implicated in neurodegenerative disease.Computational and structural biotechnology journal · 2025Article
- Emerging Alzheimer's disease therapeutics: promising insights from lipid metabolism and microglia-focused interventions.Frontiers in aging neuroscience · 2023Review
- Apolipoprotein E and Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
- Microglia and modifiable life factors: Potential contributions to cognitive resilience in aging.Behavioural brain research · 2021Review
- Investigation of pathology, expression and proteomic profiles in human TREM2 variant postmortem brains with and without Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2020Article
- Examination of the Effect of Rare Variants in TREM2, ABI3, and PLCG2 in LOAD Through Multiple Phenotypes.Journal of Alzheimer's disease : JAD · 2020Article
- The Important Interface Between Apolipoprotein E and Neuroinflammation in Alzheimer's Disease.Frontiers in immunology · 2020Review
- New insights into the role of TREM2 in Alzheimer's disease.Molecular neurodegeneration · 2018Review
- Microglia-Mediated Neuroprotection, TREM2, and Alzheimer's Disease: Evidence From Optical Imaging.Biological psychiatry · 2018Review
- TREM2 in Neurodegenerative Diseases.Molecular neurodegeneration · 2017Review
- [Search for risk genes in Alzheimer's disease].Der Nervenarzt · 2017Review
- Clearance of cerebral Aβ in Alzheimer's disease: reassessing the role of microglia and monocytes.Cellular and molecular life sciences : CMLS · 2017Review
- Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017Article
- A Missense Variant in TREML2 Reduces Risk of Alzheimer's Disease in a Han Chinese Population.Molecular neurobiology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Basavaraj V HooliFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Antonio R ParradoFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Kristina MullinFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Wai-Ki YipFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Tian LiuFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Johannes T RoehrFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Dandi QiaoFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Frank JessenFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Oliver PetersFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Tim BeckerFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Alfredo RamirezFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Christoph LangeFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Lars BertramFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany.
Rudolph E TanziFrom the MassGeneral Institute for Neurodegenerative Diseases (B.V.H., A.R.P., K.M., R.E.T.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Biostatistics (W.-K.Y., D.Q., C.L.), Harvard School of Public Health, Boston, MA; Department of Vertebrate Genomics (T.L., J.T.R., L.B.), Max Planck Institute for Molecular Genetics, Berlin; Department of Psychiatry and Psychotherapy (F.J., A.R.), Institute for Medical Biometry, Informatics and Epidemiology (T.B.), and Institute of Human Genetics (A.R.), University of Bonn; German Center for Neurodegenerative Diseases (DZNE) (F.J., T.B.), Bonn; and Department of Psychiatry (O.P.), Charité University Medicine, Berlin, Germany. tanzi@helix.mgh.harvard.edu.
Max Planck Institute for Molecular Genetics · DEHarvard University · USCenter for Human Genetics · USGerman Center for Neurodegenerative Diseases · DE
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
$119.8MTHE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1MResearch Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5MIdentification and Characterization of Novel AD GenesR37MH060009 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI TANZI, RUDOLPH EMILE · 2003 to 2012
$7.6MSEARCH FOR NOVEL EARLY-ONSET ALZHEIMER'S GENESR01AG023667 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BERTRAM, LARS · 2005 to 2007
$944kGENETIC STUDIES OF ALZHEIMERS DISEASEU01MH046281 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI ALBERT, MARILYN S · 1989 to 1997
–DIAGNOSTIC CENTERS FOR PSYCHIATRIC LINKAGE STUDIESU01MH046290 · NIMH · JOHNS HOPKINS UNIVERSITY · PI BASSETT, SUSAN SPEAR · 1989 to 1997
–ETIOLOGIC HETEROGENEITY IN FAMILIAL ALZHEIMERS DISEASEU01MH046373 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GO, RODNEY CHUN PUNG · 1989 to 1997
–NIA NIH HHS 5R01AG23667NIA NIH HHS P30 AG062421NIA NIH HHS P50 AG005134NIA NIH HHS R01 AG023667NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG21886NIMH NIH HHS 5R37MH60009NIMH NIH HHS R37 MH060009NIMH NIH HHS U01 MH46281NIMH NIH HHS U01 MH46290NIMH NIH HHS U01 MH46373
Abstract
objectivesRecently, 2 independent studies reported that a rare missense variant, rs75932628 (R47H), in exon 2 of the gene encoding the "triggering receptor expressed on myeloid cells 2" (TREM2) significantly increases the risk of Alzheimer disease (AD) with an effect size comparable to that of the APOE ε4 allele.
methodsIn this study, we attempted to replicate the association between rs75932628 and AD risk by directly genotyping rs75932628 in 2 independent Caucasian family cohorts consisting of 927 families (with 1,777 affected and 1,235 unaffected) and in 2 Caucasian case-control cohorts composed of 1,314 cases and 1,609 controls. In addition, we imputed genotypes in 3 independent Caucasian case-control cohorts containing 1,906 cases and 1,503 controls.
resultsMeta-analysis of the 2 family-based and the 5 case-control cohorts yielded a p value of 0.0029, while the overall summary estimate (using case-control data only) resulted in an odds ratio of 1.67 (95% confidence interval 0.95-2.92) for the association between the TREM2 R47H and increased AD risk.
conclusionsWhile our results serve to confirm the association between R47H and risk of AD, the observed effect on risk was substantially smaller than that previously reported.
Indexed as
Alzheimer DiseaseCase-Control StudiesGenetic Predisposition to DiseaseGenotypeHumansMembrane GlycoproteinsMutation, MissenseReceptors, ImmunologicWhite PeopleMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, human
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