ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Sex-specific genetic architecture of late-life memory performance.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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23citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% of its field
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 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
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- Genetics of educational resilience after adverse childhood experiences.EBioMedicine · 2026Article
- Multiple-testing corrections in case-control studies using identity-by-descent segments.American journal of human genetics · 2026Article
- Genetic modifiers of APOE-ε4-associated cognitive decline.Nature communications · 2026Article
- Traumatic Brain Injury and Endocytosis: Reduced Rodent Hippocampal Endocytosis Proteins and Human Clathrin Light Chain Polymorphisms Are Associated with Impaired Neurological Outcomes After TBI.Molecular neurobiology · 2026Article
- Identifying genome-by-childhood trauma interactions for depression using a forest-based approach in the UK Biobank and Adolescent Brain Cognitive Development Study.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sex differences in LDL-C genetic architecture and statin efficacy in All of Us.medRxiv : the preprint server for health sciences · 2026Article
- Precise diagnosis of Alzheimer's disease based on sex-specific gray matter characteristics.Frontiers in neuroscience · 2026Article
- Single-cell landscape of sex-specific drivers of Alzheimer's disease.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.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations.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
- Novel modelling approaches to elucidate the genetic architecture of resilience to Alzheimer's disease.Brain : a journal of neurology · 2025Article
- Multiple-testing corrections in case-control studies using identity-by-descent segments.bioRxiv : the preprint server for biology · 2025Article
- The effect of Alzheimer's disease genetic factors on limbic white matter microstructure.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
- The Role of Genetic, Environmental, and Dietary Factors in Alzheimer's Disease: A Narrative Review.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
33 authors at 11 institutions in 1 country.
Jaclyn M EissmanVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.ORCID 0000-0001-6439-3999
Derek B ArcherVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Shubhabrata MukherjeeDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Michael L LeeDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Seo-Eun ChoiDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Phoebe ScollardDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Emily H TrittschuhDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
Jesse B MezDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
William S BushCleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Brian W KunkleJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Adam C NajDepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Katherine A GiffordVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Alzheimer's Disease Neuroimaging Initiative (ADNI) | Alzheimer's Disease Genetics Consortium (ADGC) | The Alzheimer's Disease Sequencing Project (ADSP)
Michael L CuccaroJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Lindsay A FarrerDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Li-San WangPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Gerard D SchellenbergPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Richard P MayeuxColumbia University, New York, New York, USA.
Jonathan L HainesCleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Angela L JeffersonVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Walter A KukullDepartment of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
C Dirk KeeneDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Andrew J SaykinDepartment of Radiology and Imaging Services, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Paul M ThompsonKeck School of Medicine, University of Southern California, Los Angeles, California, USA.
Eden R MartinJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Lisa L BarnesRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Paul K CraneDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Timothy J HohmanVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Logan DumitrescuVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
University of Washington · USVanderbilt University Medical Center · USUniversity of Miami · USRush University Medical Center · USUniversity of Pennsylvania · USBoston University · USCase Western Reserve University · USIndiana University School of MedicineNewYork–Presbyterian Hospital · USUniversity of Southern California · USWashington University in St. Louis · US
Funding
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI Duygu Tosun-Turgut · 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
$119.8MTranslational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI Christine L MacDonald · 2021 to 2026
$80.4MNATIONAL 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 JOHN MORRIS · 1985 to 2026
$69.5MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MNational 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
$43.3MTREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SWEET, ROBERT A · 1985 to 2019
$43.0MNCATS NIH HHS UL1 TR000445NHGRI NIH HHS U01 HG004610NIA NIH HHS F31 AG077791NIA NIH HHS K01 AG049164NIA NIH HHS K01 AG073584NIA NIH HHS K23 AG045966NIA NIH HHS K24 AG046373NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P20 AG068024NIA NIH HHS P20 AG068053NIA NIH HHS P20 AG068077NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG034962NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG042210NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG048015NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG056534NIA NIH HHS R01 AG059716NIA NIH HHS R01 AG061518NIA NIH HHS R01 AG062634NIA NIH HHS R01 AG064614NIA NIH HHS R01 AG064877NIA NIH HHS R01 AG067501NIA NIH HHS R01 AG073439NIA NIH HHS R01 AG079280NIA NIH HHS R21 AG059941NIA NIH HHS RC2 AG036528NIA NIH HHS RC2 AG036547NIA NIH HHS RC2 AG036650NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG054080NIA NIH HHS RF1 AG057473NIA NIH HHS RF1 AG058501NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG052410NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG058922NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG068057NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG066567NIA NIH HHS U19 AG068753NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NIA NIH HHS U24 AG072122NIA NIH HHS U24 AG074855NIA NIH HHS U54 AG052427NICHD NIH HHS K12 HD043483NIH HHS F31 AG077791NIH HHS HHSN311201600276PNIH HHS K01 AG049164NIH HHS K12 HD043483NIH HHS K23 AG045966NIH HHS K24 AG046373NIH HHS P01 AG003991NIH HHS P01 AG026276NIH HHS P20 AG068024NIH HHS P20 AG068053NIH HHS P20 AG068077NIH HHS P20 AG068082NIH HHS P30 AG010161NIH HHS P30 AG062421NIH HHS P30 AG062422NIH HHS P30 AG062429NIH HHS P30 AG062677NIH HHS P30 AG062715NIH HHS P30 AG066444NIH HHS P30 AG066462NIH HHS P30 AG066468NIH HHS P30 AG066506NIH HHS P30 AG066507NIH HHS P30 AG066508NIH HHS P30 AG066509NIH HHS P30 AG066511NIH HHS P30 AG066512NIH HHS P30 AG066514NIH HHS P30 AG066515NIH HHS P30 AG066518NIH HHS P30 AG066519NIH HHS P30 AG066530NIH HHS P30 AG066546NIH HHS P30 AG072931NIH HHS P30 AG072946NIH HHS P30 AG072947NIH HHS P30 AG072958NIH HHS P30 AG072959NIH HHS P30 AG072972NIH HHS P30 AG072973NIH HHS P30 AG072975NIH HHS P30 AG072976NIH HHS P30 AG072977NIH HHS P30 AG072978NIH HHS P30 AG072979NIH HHS P30 AG079280NIH HHS R01 AG015819NIH HHS R01 AG017917NIH HHS R01 AG022018NIH HHS R01 AG030146NIH HHS R01 AG034962NIH HHS R01 AG036042NIH HHS R01 AG036836NIH HHS R01 AG044546NIH HHS R01 AG048015NIH HHS R01 AG048927NIH HHS R01 AG056534NIH HHS R01 AG059716NIH HHS R01 AG061518NIH HHS R01 AG062634NIH HHS R01 AG064614NIH HHS R01 AG064877NIH HHS R01 AG073439NIH HHS R01 AG42210NIH HHS R01 NS100980NIH HHS R21 AG059941NIH HHS RC2 AG036528NIH HHS RC2 AG036547NIH HHS RF1 AG053303NIH HHS RF1 AG054080NIH HHS RF1 AG057473NIH HHS RF1 AG058501NIH HHS S10 OD023680NIH HHS U01 AG006781NIH HHS U01 AG016976NIH HHS U01 AG024904NIH HHS U01 AG032984NIH HHS U01 AG046152NIH HHS U01 AG046161NIH HHS U01 AG052410NIH HHS U01 AG058654NIH HHS U01 AG058922NIH HHS U01 AG061356NIH HHS U01 AG068057NIH HHS U19 AG066567NIH HHS U19 AG068753NIH HHS U24 AG021886NIH HHS U24 AG041689NIH HHS U24 AG056270NIH HHS U24 AG072122NIH HHS U24 AG074855NIH HHS U54 AG052427NIH HHS UL1 TR000445NINDS NIH HHS R01 NS100980
Abstract
backgroundWomen demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear.
methodsWe conducted the largest sex-aware genetic study on late-life memory to date (N
resultsWe identified three sex-specific loci (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633-EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-specific pathway and found sex-specific genetic correlations between memory and cardiovascular, immune, and education traits. DISCUSSION: This study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex-specific genes, pathways, and genetic correlations that related to late-life memory. HIGHLIGHTS: Demonstrated the heritable component of late-life memory is similar across sexes. Identified two genetic loci with a sex-interaction with baseline memory. Identified an X-chromosome locus associated with memory decline in females. Highlighted sex-specific candidate genes and pathways associated with memory. Revealed sex-specific shared genetic architecture between memory and complex traits.
Indexed as
Alzheimer DiseaseCognitive AgingCognitionFemaleGenome-Wide Association StudyHumansMaleSex CharacteristicsagingAlzheimer's diseasecognitionendophenotypesGenomicsGWASmemorysex differencessex-specific
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