ArticleNature neuroscience2017
A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease.
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In one paragraph
Article in Nature neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers, 11 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
275citing papers in PubMed, 11 pooled it
20.8field-weighted citation impact, top 1% of its field
What it found
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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
275 citing papers in PubMed, 11 syntheses or guidelines pooled it, 463 citations in OpenAlex.
- Pooled it
- Pooled it
- GhostKnockoff inference empowers identification of putative causal variants in genome-wide association studies.Nature communications · 2022Pooled it
- Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies.Nature genetics · 2022Pooled it
- Genetically regulated expression in late-onset Alzheimer's disease implicates risk genes within known and novel loci.Translational psychiatry · 2021Pooled it
- Using Mendelian randomization analysis to better understand the relationship between mental health and substance use: a systematic review.Psychological medicine · 2021Pooled it
- Sex-specific DNA methylation differences in Alzheimer's disease pathology.Acta neuropathologica communications · 2021Pooled it
- Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review.Frontiers in aging neuroscience · 2021Pooled it
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer's disease.Nature communications · 2020Pooled it
- Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty.PLoS genetics · 2020Pooled it
- Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Review
- Robust Inference With Ghostknockoffs in Genome-Wide Association Studies With Sample Relatedness.Genetic epidemiology · 2026Article
- Article
- KOLF2.1J iTF-Microglia: A standardized platform to study microglial transcriptional regulatory networks in CNS disease.iScience · 2026Article
- CIT-Lasso: a scalable approach beyond guilty by association for identifying causal variants from genome-wide summary statistics.Genome biology · 2026Article
- Lymphoid-like Suppressive Microglia in Alzheimer's Disease: A New Neuroimmune Regulatory Axis?Cells · 2026Review
- Depletion of microglial compensation in glial network: Disease-associated response dynamics in the revised amyloid hypothesis.Neuroprotection (Chichester, England) · 2026Review
- Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.Nature communications · 2026Article
215 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
49 authors at 16 institutions in 5 countries.
Kuan-Lin HuangDepartment of Medicine and McDonnell Genome Institute, Washington University in St. Louis, Saint Louis, Missouri, USA.
Edoardo MarcoraDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.ORCID http://orcid.org/0000-0002-3829-4927
Anna A PimenovaRonald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Antonio F Di NarzoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Manav KapoorDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Sheng Chih JinDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Oscar HarariDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.
Sarah BertelsenRonald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Benjamin P FairfaxWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Jake CzajkowskiDepartment of Genetics, Washington University in St. Louis, Saint Louis, Missouri, USA.
Vincent ChourakiDepartment of Neurology, Boston University School of Medicine, Boston, Massachussets, USA.
Benjamin Grenier-BoleyInserm, U1167, RID-AGE -Risk factors and molecular determinants of aging-related diseases, Lille, France.
Céline BellenguezInserm, U1167, RID-AGE -Risk factors and molecular determinants of aging-related diseases, Lille, France.
Yuetiva DemingDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.ORCID http://orcid.org/0000-0001-7512-5703
Andrew McKenzieDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Towfique RajDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Alan E RentonRonald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
John BuddeDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.
Albert SmithIcelandic Heart Association, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-1942-5845
Annette FitzpatrickDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Joshua C BisDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Anita DeStefanoDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachussetts, USA.
Hieab H H AdamsDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-3687-2508
M Arfan IkramDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-0372-8585
Sven van der LeeDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-1606-8643
Jorge L Del-AguilaDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.
Maria Victoria FernandezDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.
Laura IbañezDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.ORCID http://orcid.org/0000-0003-2381-7059
International Genomics of Alzheimer's Project
Alzheimer's Disease Neuroimaging Initiative
Rebecca SimsPsychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Valentina Escott-PricePsychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Richard MayeuxTaub Institute on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, and Department of Neurology, Columbia University, New York,New York, USA.
Jonathan L HainesDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
Lindsay A FarrerDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachussetts, USA.
Margaret A Pericak-VanceThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Jean Charles LambertInserm, U1167, RID-AGE -Risk factors and molecular determinants of aging-related diseases, Lille, France.ORCID http://orcid.org/0000-0003-0829-7817
Cornelia van DuijnDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Lenore LaunerLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA.
Sudha SeshadriDepartment of Neurology, Boston University School of Medicine, Boston, Massachussets, USA.
Julie WilliamsPsychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Philippe AmouyelInserm, U1167, RID-AGE -Risk factors and molecular determinants of aging-related diseases, Lille, France.ORCID http://orcid.org/0000-0001-9088-234X
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Ingrid BoreckiDepartment of Genetics, Washington University in St. Louis, Saint Louis, Missouri, USA.
John S K KauweDepartment of Biology, Brigham Young University, Provo, Utah, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.ORCID http://orcid.org/0000-0002-0276-2899
Ke HaoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.
Alison M GoateDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,New York, USA.ORCID http://orcid.org/0000-0002-0576-2472
Washington University in St. Louis · USBoston University · USIcahn School of Medicine at Mount Sinai · USInserm · FRBrigham Young University · USJames S. McDonnell Foundation · USUniversity of Iceland · ISUniversity of Miami · USUniversity of Washington · USYale University · USCardiff University · GBCase Western Reserve University · USCentre for Human Genetics · GBColumbia University · USErasmus MC · NLNational Institute on Aging · US
Funding
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MICHAEL W WEINER · 2016 to 2026
$226.7MAlzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MNational 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
$119.8MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2005 to 2025
$49.5MVESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHIMMING, CORBETT · 1985 to 2019
$37.9MIdentification and characterization of AD risk networks using multi-dimensional "omics" dataU01AG052411 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2016 to 2020
$4.5MCollaborative GWAS of Dementia, AD and related MRI and Cognitive EndophenotypesR01AG033193 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2016
$4.4MRESEARCH EDUCATION PROGRAM ON COMPUTATIONAL AND STATISTICAL TOOL DEVELOPMENT FOR ADDICTION GENETICSR25DA027995 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN, RICE, JOHN P. · 2009 to 2019
$4.3MUnderstanding the mechanism of SPl1 dependent Alzheimer disease riskRF1AG054011 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GOATE, ALISON M · 2016 to 2016
$4.2MIntramural NIH HHS Z99 AG999999Medical Research Council G0300429Medical Research Council MC_PC_17112Medical Research Council MR/L010305/1Medical Research Council MR/L023784/1Medical Research Council MR/L023784/2Medical Research Council MR/P005748/1NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005681NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG035083NIA NIH HHS R01 AG044546NIA NIH HHS RF1 AG044546NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG054011NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049508NIA NIH HHS U01 AG052411NIA NIH HHS U19 AG024904NIA NIH HHS U24 AG021886NIDA NIH HHS R25 DA027995Wellcome Trust 201488/Z/16/Z
Abstract
A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function.
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyAllelesAlzheimer DiseaseAnimalsFemaleHaplotypesHumansLinkage DisequilibriumMaleMicePolymorphism, Single NucleotideProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Risk FactorsTrans-ActivatorsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-ActivatorsTranscription Factors
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