ArticleBrain : a journal of neurology2019
Sex differences in the genetic predictors of Alzheimer's pathology.
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In one paragraph
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
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65citing papers in PubMed, 4 pooled it
9.9field-weighted citation impact, top 1% of its field
What it found
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Who cites it
65 citing papers in PubMed, 4 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled 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
- Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.Gastroenterology · 2020Pooled it
- 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
- Identifying sex-specific sub-phenotypes of Alzheimer's disease progression using longitudinal electronic health records.EBioMedicine · 2026Article
- Widespread and Biologically Driven Sex Disparities in Polygenic Risk Prediction Across Complex Traits.Research square · 2026Article
- Sex-stratified genetic regulators of cytokine production in the Dutch and Tanzanian populations.HGG advances · 2026Article
- AI guided discovery of a murine model of asymptomatic Alzheimer's disease.Acta neuropathologica communications · 2026Article
- Transcriptional mechanisms of sex-biased gene expression and their connections to disease-associated variation.Human molecular genetics · 2026Article
- Sex-dependent grey matter atrophy in Alzheimer's disease progression.Brain communications · 2026Article
- Single-cell landscape of sex-specific drivers of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrative Genetic, Proteogenomic, and Multi-omics Analyses Reveal Sex-Biased Causal Genes and Drug Targets in Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2025Article
- Genetic regulation of the metabolome differs by sex, Alzheimer's disease stage, and plasma biomarker status.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Identifying Sex-Specific Sub-phenotypes of Alzheimer's Disease Progression Using Longitudinal Electronic Health Records.medRxiv : the preprint server for health sciences · 2025Article
- Leveraging multiomic approaches to elucidate mechanisms of heterogeneity in Alzheimer's disease: Neuropsychiatric symptoms, co-pathologies, and sex differences.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Dementia Deaths Most Commonly Result from Heart and Lung Disease: Evidence from the South Carolina Alzheimer's Disease Registry.Biomedicines · 2025Article
- Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Genetic Regulation of the Metabolome Differs by Sex, Alzheimer's Disease Stage, and Plasma Biomarker Status.medRxiv : the preprint server for health sciences · 2025Article
- Sex chromosomes and gonads modify microglial-mediated pathology in a mouse model of Alzheimer's disease.Journal of neuroinflammation · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
39 authors at 17 institutions in 3 countries.
Logan DumitrescuVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Lisa L BarnesRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Madhav ThambisettyLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Gary BeechamJohn T MacDonald Foundation Department of Human Genetics, University of Miami, Miami, FL, USA.
Brian KunkleJohn P. Hussman Institute for Human Genomics, University of Miami School of Medicine, Miami, FL, USA.
William S BushDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Katherine A GiffordVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Lori B ChibnikDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Shubhabrata MukherjeeDepartment of Medicine, University of Washington, Seattle, WA, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Walter KukullDepartment of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Paul K CraneDepartment of Medicine, University of Washington, Seattle, WA, USA.
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
C Dirk KeeneDepartment of Pathology, University of Washington, Seattle, WA, USA.
Thomas J MontineDepartment of Pathology, Stanford University, Stanford, CA, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yuetiva DemingDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Michael J ChaoRonald M Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Matt HuentelmanNeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
Eden R MartinJohn T MacDonald Foundation Department of Human Genetics, University of Miami, Miami, FL, USA.
Kara Hamilton-NelsonJohn P. Hussman Institute for Human Genomics, University of Miami School of Medicine, Miami, FL, USA.
Leslie M ShawDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John Q TrojanowskiDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Elaine R PeskindDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami School of Medicine, Miami, FL, USA.
Alison M GoateRonald M Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nancy J CoxVanderbilt Genetics Institute, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Eric B LarsonDepartment of Medicine, University of Washington, Seattle, WA, USA.
Sterling C JohnsonAlzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Marilyn AlbertDepartment of Neurology, the Johns Hopkins University School of Medicine, Baltimore, MD.
Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Neuroimaging Initiative
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Angela L JeffersonVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
University of Washington · USVanderbilt University Medical Center · USUniversity of Miami · USRush University Medical Center · USUniversity of Pennsylvania · USCase Western Reserve University · USIcahn School of Medicine at Mount Sinai · USNational Institute on Aging · USSahlgrenska University Hospital · SEWashington University in St. Louis · USBroad Institute · USDr. John T. Macdonald Foundation · USHarvard University · USJohns Hopkins Medicine · USStanford University · USTranslational Genomics Research Institute · USUniversity of Wisconsin–Madison · 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
$119.8MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Suzanne Elizabeth Schindler · 1985 to 2026
$69.5MAlzheimer'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 GRABOWSKI, THOMAS J. · 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 FAGAN, ANNE · 1985 to 2019
$52.1MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MTREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMBOH, M. ILYAS · 1985 to 2019
$43.0MTHE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3MNCATS NIH HHS KL2 TR000446NCATS NIH HHS TL1 TR000447NCATS NIH HHS UL1 TR000445NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG006375NHLBI NIH HHS R01 HL111516NIA NIH HHS K01 AG049164NIA NIH HHS K24 AG046373NIA NIH HHS K25 AG055620NIA NIH HHS P01 AG003991NIA 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 AG035982NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072973NIA 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 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG021155NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG034962NIA NIH HHS R01 AG035083NIA NIH HHS R01 AG037639NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG048015NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG056534NIA NIH HHS R01 AG059716NIA NIH HHS R21 AG059941NIA NIH HHS RF1 AG015819NIA NIH HHS RF1 AG027161NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG057519NIA NIH HHS RF1 AG058501NIA NIH HHS T32 AG000213NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG058654NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NICHD NIH HHS K12 HD043483NICHD NIH HHS U54 HD083211NIH HHS S10 OD023680NIMH NIH HHS T32 MH014677NINDS NIH HHS R01 NS085419NINDS NIH HHS R01 NS100980NINDS NIH HHS UH3 NS100605
Abstract
Autopsy measures of Alzheimer's disease neuropathology have been leveraged as endophenotypes in previous genome-wide association studies (GWAS). However, despite evidence of sex differences in Alzheimer's disease risk, sex-stratified models have not been incorporated into previous GWAS analyses. We looked for sex-specific genetic associations with Alzheimer's disease endophenotypes from six brain bank data repositories. The pooled dataset included 2701 males and 3275 females, the majority of whom were diagnosed with Alzheimer's disease at autopsy (70%). Sex-stratified GWAS were performed within each dataset and then meta-analysed. Loci that reached genome-wide significance (P < 5 × 10-8) in stratified models were further assessed for sex interactions. Additional analyses were performed in independent datasets leveraging cognitive, neuroimaging and CSF endophenotypes, along with age-at-onset data. Outside of the APOE region, one locus on chromosome 7 (rs34331204) showed a sex-specific association with neurofibrillary tangles among males (P = 2.5 × 10-8) but not females (P = 0.85, sex-interaction P = 2.9 × 10-4). In follow-up analyses, rs34331204 was also associated with hippocampal volume, executive function, and age-at-onset only among males. These results implicate a novel locus that confers male-specific protection from tau pathology and highlight the value of assessing genetic associations in a sex-specific manner.
Indexed as
Sex CharacteristicsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesCohort StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePolymorphism, Single Nucleotidetau ProteinsAmyloid beta-PeptidesMAPT protein, humantau ProteinsAlzheimer’s diseasebeta-amyloidgenome-wide association studyneuropathologytau
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