Sex-specific genetic architecture of late-life memory performance

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dc.contributor.authorEissman, Jaclyn M.
dc.contributor.authorArcher, Derek B.
dc.contributor.authorMukherjee, Shubhabrata
dc.contributor.authorLee, Michael L.
dc.contributor.authorChoi, Seo-Eun
dc.contributor.authorScollard, Phoebe
dc.contributor.authorTrittschuh, Emily H.
dc.contributor.authorMez, Jesse B.
dc.contributor.authorBush, William S.
dc.contributor.authorKunkle, Brian W.
dc.contributor.authorNaj, Adam C.
dc.contributor.authorGifford, Katherine A.
dc.contributor.authorAlzheimer's Disease Neuroimaging Initiative (ADNI)
dc.contributor.authorAlzheimer's Disease Genetics Consortium (ADGC)
dc.contributor.authorThe Alzheimer's Disease Sequencing Project (ADSP)
dc.contributor.authorCuccaro, Michael L.
dc.contributor.authorCruchaga, Carlos
dc.contributor.authorPericak-Vance, Margaret A.
dc.contributor.authorFarrer, Lindsay A.
dc.contributor.authorWang, Li-San
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorMayeux, Richard P.
dc.contributor.authorHaines, Jonathan L.
dc.contributor.authorJefferson, Angela L.
dc.contributor.authorKukull, Walter A.
dc.contributor.authorKeene, C. Dirk
dc.contributor.authorSaykin, Andrew J.
dc.contributor.authorThompson, Paul M.
dc.contributor.authorMartin, Eden R.
dc.contributor.authorBennett, David A.
dc.contributor.authorBarnes, Lisa L.
dc.contributor.authorSchneider, Julie A.
dc.contributor.authorCrane, Paul K.
dc.contributor.authorHohman, Timothy J.
dc.contributor.authorDumitrescu, Logan
dc.contributor.departmentRadiology and Imaging Sciences, School of Medicine
dc.date.accessioned2024-06-27T09:59:57Z
dc.date.available2024-06-27T09:59:57Z
dc.date.issued2024
dc.description.abstractBackground: 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. Methods: We conducted the largest sex-aware genetic study on late-life memory to date (Nmales = 11,942; Nfemales = 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. Results: 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. 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.
dc.eprint.versionFinal published version
dc.identifier.citationEissman JM, Archer DB, Mukherjee S, et al. Sex-specific genetic architecture of late-life memory performance. Alzheimers Dement. 2024;20(2):1250-1267. doi:10.1002/alz.13507
dc.identifier.urihttps://hdl.handle.net/1805/41942
dc.language.isoen_US
dc.publisherWiley
dc.relation.isversionof10.1002/alz.13507
dc.relation.journalAlzheimer's & Dementia
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcePMC
dc.subjectAlzheimer's disease
dc.subjectGWAS
dc.subjectGenomics
dc.subjectAging
dc.subjectCognition
dc.subjectEndophenotypes
dc.subjectMemory
dc.subjectSex differences
dc.subjectSex-specific
dc.titleSex-specific genetic architecture of late-life memory performance
dc.typeArticle
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