Sex-Specific Genetic Drivers of Memory, Executive Functioning, and Language Performance in Older Adults
dc.contributor.author | Eissman, Jaclyn M. | |
dc.contributor.author | Regelson, Alexandra N. | |
dc.contributor.author | Walters, Skylar | |
dc.contributor.author | Archer, Derek B. | |
dc.contributor.author | Durant, Alaina | |
dc.contributor.author | Mukherjee, Shubhabrata | |
dc.contributor.author | Lee, Michael L. | |
dc.contributor.author | Choi, Seo-Eun | |
dc.contributor.author | Scollard, Phoebe | |
dc.contributor.author | Trittschuh, Emily H. | |
dc.contributor.author | Mez, Jesse | |
dc.contributor.author | Kang, Moonil | |
dc.contributor.author | Bush, William S. | |
dc.contributor.author | Kunkle, Brian W. | |
dc.contributor.author | Naj, Adam C. | |
dc.contributor.author | Gifford, Katherine A. | |
dc.contributor.author | Bilgel, Murat | |
dc.contributor.author | Kuzma, Amanda B. | |
dc.contributor.author | Alzheimer’s Disease Neuroimaging Initiative (ADNI) | |
dc.contributor.author | Alzheimer’s Disease Genetics Consortium (ADGC) | |
dc.contributor.author | Alzheimer’s Disease Sequencing Project (ADSP) | |
dc.contributor.author | Cuccaro, Michael L. | |
dc.contributor.author | Cruchaga, Carlos | |
dc.contributor.author | Pericak-Vance, Margaret A. | |
dc.contributor.author | Farrer, Lindsay A. | |
dc.contributor.author | Wang, Li-San | |
dc.contributor.author | Schellenberg, Gerard D. | |
dc.contributor.author | Vardarajan, Badri N. | |
dc.contributor.author | Mayeux, Richard | |
dc.contributor.author | Haines, Jonathan L. | |
dc.contributor.author | Jefferson, Angela L. | |
dc.contributor.author | Kukull, Walter A. | |
dc.contributor.author | Keene, C. Dirk | |
dc.contributor.author | Saykin, Andrew J. | |
dc.contributor.author | Thompson, Paul M. | |
dc.contributor.author | Martin, Eden R. | |
dc.contributor.author | Albert, Marilyn S. | |
dc.contributor.author | Johnson, Sterling C. | |
dc.contributor.author | Engelman, Corinne D. | |
dc.contributor.author | Ferrucci, Luigi | |
dc.contributor.author | Bennett, David A. | |
dc.contributor.author | Barnes, Lisa L. | |
dc.contributor.author | Schneider, Julie A. | |
dc.contributor.author | Resnick, Susan M. | |
dc.contributor.author | Sperling, Reisa A. | |
dc.contributor.author | Crane, Paul K. | |
dc.contributor.author | Hohman, Timothy J. | |
dc.contributor.author | Dumitrescu, Logan | |
dc.contributor.department | Radiology and Imaging Sciences, School of Medicine | |
dc.date.accessioned | 2025-07-14T15:12:19Z | |
dc.date.available | 2025-07-14T15:12:19Z | |
dc.date.issued | 2025-06-02 | |
dc.description.abstract | We previously identified sex-specific genetic loci associated with memory performance, a strong Alzheimer's disease (AD) endophenotype. Here, we expand on this work by conducting sex-specific, cross-ancestral, genome-wide meta-analyses of three cognitive domains (memory, executive functioning, and language) in 33,918 older adults (57% female; 41% cognitively impaired; mean age=73 years) from 10 aging and AD cohorts. All three domains were comparably heritable across sexes. Genome-wide meta-analyses identified three novel loci: a female-specific language decline-associated locus, VRK2 (rs13387871), which is a published candidate for neuropsychiatric traits involving language ability; a male-specific memory decline-associated locus among cognitive impaired, DCHS2 (rs12501200), which is a published candidate gene for AD age-at-onset; and a sex-interaction with baseline executive functioning, AGA (rs1380012), among cognitive impaired. We additionally provide evidence for shared genetic architecture between lifetime estrogen exposure and AD-related cognitive decline. Overall, we identified sex-specific variants, genes, and pathways relating to three cognitive domains among older adults. | |
dc.eprint.version | Preprint | |
dc.identifier.citation | Eissman JM, Regelson AN, Walters S, et al. Sex-Specific Genetic Drivers of Memory, Executive Functioning, and Language Performance in Older Adults. Preprint. medRxiv. 2025;2025.05.26.25328369. Published 2025 Jun 2. doi:10.1101/2025.05.26.25328369 | |
dc.identifier.uri | https://hdl.handle.net/1805/49429 | |
dc.language.iso | en_US | |
dc.publisher | medRxiv | |
dc.relation.isversionof | 10.1101/2025.05.26.25328369 | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | PMC | |
dc.subject | Sex-specific genetic loci | |
dc.subject | Memory performance | |
dc.subject | Alzheimer's disease (AD) endophenotype | |
dc.title | Sex-Specific Genetic Drivers of Memory, Executive Functioning, and Language Performance in Older Adults | |
dc.type | Article |