ArticleNature genetics2024
GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia.
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Article in Nature genetics, 2024. 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 57 papers, 4 of them syntheses that pooled it.
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57citing papers in PubMed, 4 pooled it
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Who cites it
57 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer's disease and related dementias in a multi-site autopsy cohort.PLoS genetics · 2026Pooled it
- Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias.Nature genetics · 2026Pooled it
- Disentangling the inverse relationship between cancer and Alzheimer's or Parkinson's disease: A systematic review on Mendelian randomization studies.Neurobiology of disease · 2025Pooled it
- Systematic review and meta-analysis of bulk RNAseq studies in human Alzheimer's disease brain tissue.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- APOE-stratified genome-wide association analyses provide insights into the genetic etiology of Alzheimers's disease.Nature genetics · 2026Article
- Integrative prediction of Alzheimer's disease and related dementias using multi-omics aging clocks and genetic data.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Observational
- A new era of genome-wide association studies in the field of Alzheimer's disease and overlapping co-pathologies: lessons learned from a neuropathology-centered approach.Acta neuropathologica · 2026Review
- IsoformSwitchAnalyzeR v2: analysis of functional isoform changes in long-read and single-cell sequencing data.NAR genomics and bioinformatics · 2026Article
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Systematic contextual biases in SegmentNT potentially relevant to other nucleotide transformer models.Nucleic acids research · 2026Article
- Predicting accumulation and age at onset of amyloid-β from genetic risk and resilience for Alzheimer's disease.EBioMedicine · 2026Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Dissecting Alzheimer's disease heterogeneity by cross-trait polygenic prediction.bioRxiv : the preprint server for biology · 2026Article
- Sex-dependent interferon signaling contributes to female-biased vulnerability in Alzheimer's disease.Journal of neuroinflammation · 2026Article
- Systematic contextual biases in SegmentNT potentially relevant to other nucleotide transformer models.bioRxiv : the preprint server for biology · 2026Article
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- Genetic drivers of progression in Alzheimer's disease are distinct from disease risk.Alzheimer's research & therapy · 2026Article
- Progranulin genetic variant rs5848 displays ancestry-specific associations with Alzheimer's disease.Human genomics · 2026Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
25 authors.
Lincoln M P ShadeDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.
Yuriko KatsumataDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0002-0188-8094
Erin L AbnerSanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA.
Khine Zin AungDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0009-0000-3793-6927
Steven A ClaasDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0001-9789-8395
Qi QiaoDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.
Bernardo Aguzzoli HeberleSanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0002-6177-9316
J Anthony BrandonSanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA.
Madeline L PageSanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0001-9990-1500
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-3377-7014
Shubhabrata MukherjeeDepartment of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-2522-2884
Richard P MayeuxDepartment of Neurology, Columbia University, New York City, NY, USA.ORCID http://orcid.org/0000-0001-6519-9696
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5533-4225
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Jonathan L HainesCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Walter A KukullNational Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-8761-9014
Kwangsik NhoDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Andrew J SaykinIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-1376-8532
David A BennettDepartment of Neurological Sciences, Rush Medical College, Chicago, IL, USA.
Julie A SchneiderDepartment of Neurological Sciences, Rush Medical College, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-9482-1752
National Alzheimer’s Coordinating Center
Alzheimer’s Disease Genetics Consortium
Mark T W EbbertSanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0001-9158-4440
Peter T NelsonSanders-Brown Center on Aging and Alzheimer's Disease Research Center, University of Kentucky, Lexington, KY, USA.
David W FardoDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA. david.fardo@uky.edu.ORCID http://orcid.org/0000-0002-7207-4696
Funding
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI ARTHUR W TOGA · 2016 to 2026
$226.7MNational 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
$119.8MTranslational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI Paul K Crane, Andrea Z. LaCroix · 2021 to 2026
$80.4MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI JAYADEY, SUMAN · 1985 to 2019
$57.2MVIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MNational Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MNIA NIH HHS K25 AG055620NIA NIH HHS P01 AG078116NIA 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 AG028383NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG049638NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072980NIA 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 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS P50 AG047266NIA NIH HHS P50 AG047270NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG033678NIA NIH HHS R01 AG034374NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG040039NIA NIH HHS R01 AG042210NIA NIH HHS R01 AG043379NIA NIH HHS R01 AG047976NIA NIH HHS R01 AG056352NIA NIH HHS R01 AG061111NIA NIH HHS R01 AG068331NIA NIH HHS R01 AG082730NIA NIH HHS R56 AG057191NIA NIH HHS RC2 AG036528NIA NIH HHS RF1 AG054057NIA NIH HHS RF1 AG082339NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG068057NIA NIH HHS U01 AG072177NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG066567NIA NIH HHS U19 AG074879NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG072122NIGMS NIH HHS R35 GM138636NINDS NIH HHS F30 NS124136NINDS NIH HHS R01 NS078009NINDS NIH HHS RF1 NS118584NINDS NIH HHS U01 NS100599NINDS NIH HHS UH2 NS100599NLM NIH HHS R01 LM012535U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) RF1AG082339
Abstract
Genome-wide association studies (GWAS) have identified >80 Alzheimer's disease and related dementias (ADRD)-associated genetic loci. However, the clinical outcomes used in most previous studies belie the complex nature of underlying neuropathologies. Here we performed GWAS on 11 ADRD-related neuropathology endophenotypes with participants drawn from the following three sources: the National Alzheimer's Coordinating Center, the Religious Orders Study and Rush Memory and Aging Project, and the Adult Changes in Thought study (n = 7,804 total autopsied participants). We identified eight independent significantly associated loci, of which four were new (COL4A1, PIK3R5, LZTS1 and APOC2). Separately testing known ADRD loci, 19 loci were significantly associated with at least one neuropathology after false-discovery rate adjustment. Genetic colocalization analyses identified pleiotropic effects and quantitative trait loci. Methylation in the cerebral cortex at two sites near APOC2 was associated with cerebral amyloid angiopathy. Studies that include neuropathology endophenotypes are an important step in understanding the mechanisms underlying genetic ADRD risk.
Indexed as
Alzheimer DiseaseDementiaEndophenotypesGenetic Predisposition to DiseaseGenome-Wide Association StudyQuantitative Trait LociAgedAged, 80 and overFemaleHumansMaleNeuropathologyPolymorphism, Single NucleotideRisk Factors
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