{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Eissman JM"],"funding":["NCATS NIH HHS","NICHD NIH HHS","NIA NIH HHS","U.S. Department of Defense","NHGRI NIH HHS","NINDS NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["1250-1267"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10917043"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(2)"],"pubmed_abstract":["<h4>Background</h4>Women 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.<h4>Methods</h4>We conducted the largest sex-aware genetic study on late-life memory to date (N<sub>males</sub>  = 11,942; N<sub>females</sub>  = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants.<h4>Results</h4>We 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.<h4>Discussion</h4>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.<h4>Highlights</h4>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."],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["Sex-specific genetic architecture of late-life memory performance."],"pmcid":["PMC10917043"],"funding_grant_id":["K12 HD043483","U19 AG024904","R01 AG019085","P20 AG068053","R01 AG073439","P30 AG066444","R01 AG022018","R01 AG048927","R01 AG064614","RF1 AG054080","P30 AG072958","P30 AG072959","R01 AG030146","P30 AG066546","K23 AG045966","RF1 AG058501","RF1 AG053303","R01 AG42210","R01 AG048015","U01 AG032984","HHSN311201600276P","U24 AG041689","P30 AG072946","P30 AG072947","P01 AG003991","U19 AG066567","R01 AG036836","U24 AG021886","P30 AG072931","P20 AG068077","R01 AG044546","U01 AG046152","R01 AG056534","P30 AG079280","U01 AG068057","F31 AG077791","P30 AG066530","P20 AG068082","U01 AG046161","S10 OD023680","U24 AG056270","R01 AG017917","U01 AG058654","P30 AG062677","K01 AG073584","P30 AG066514","P30 AG066515","P30 AG066518","P30 AG062715","P30 AG066519","U01 AG058922","R01 AG062634","U19 AG068753","U54 AG052427","P30 AG062421","P30 AG062422","P30 AG010161","UL1 TR000445","P30 AG066506","P30 AG066507","P30 AG062429","P30 AG066508","P30 AG066509","R01 AG036042","RC2 AG036547","P30 AG066511","P30 AG066512","U24 AG072122","P20 AG068024","U01 AG052410","R01 AG061518","R01 AG015819","U01 AG061356","W81XWH‐12‐2‐0012","R01 AG059716","U01 AG006781","P30 AG072975","P30 AG066462","P30 AG072976","P30 AG072977","R21 AG059941","U24 AG074855","P30 AG072972","P30 AG072973","P30 AG066468","R01 AG064877","P30 AG072978","RC2 AG036650","R01 AG079280","P30 AG072979","K24 AG046373","K01 AG049164","U01 HG004610","U01 AG016976","RF1 AG057473","R01 NS100980","R01 AG034962","RC2 AG036528","P01 AG026276","U01 AG024904","R01 AG042210"],"pubmed_authors":["Barnes LL","Scollard P","Jefferson AL","Martin ER","Naj AC","Schellenberg GD","Kukull WA","Haines JL","Cuccaro ML","Pericak-Vance MA","Eissman JM","Farrer LA","Saykin AJ","Dumitrescu L","Mayeux RP","Wang LS","Crane PK","Hohman TJ","Kunkle BW","Cruchaga C","Archer DB","Bush WS","Alzheimer's Disease Neuroimaging Initiative (ADNI) | Alzheimer's Disease Genetics Consortium (ADGC) | The Alzheimer's Disease Sequencing Project (ADSP)","Bennett DA","Schneider JA","Choi SE","Gifford KA","Mukherjee S","Trittschuh EH","Mez JB","Thompson PM","Keene CD","Lee ML"],"additional_accession":[]},"is_claimable":false,"name":"Sex-specific genetic architecture of late-life memory performance.","description":"<h4>Background</h4>Women 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.<h4>Methods</h4>We conducted the largest sex-aware genetic study on late-life memory to date (N<sub>males</sub>  = 11,942; N<sub>females</sub>  = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants.<h4>Results</h4>We 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.<h4>Discussion</h4>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.<h4>Highlights</h4>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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-05-29T15:16:00.56Z","creation":"2026-04-08T05:13:20.066Z"},"accession":"S-EPMC10917043","cross_references":{"pubmed":["37984853"],"doi":["10.1002/alz.13507"]}}