Browsing by Author "The Alzheimer's Disease Sequencing Project (ADSP)"

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    Sex-specific genetic architecture of late-life memory performance
    (Wiley, 2024) Eissman, Jaclyn M.; Archer, Derek B.; Mukherjee, Shubhabrata; Lee, Michael L.; Choi, Seo-Eun; Scollard, Phoebe; Trittschuh, Emily H.; Mez, Jesse B.; Bush, William S.; Kunkle, Brian W.; Naj, Adam C.; Gifford, Katherine A.; Alzheimer's Disease Neuroimaging Initiative (ADNI); Alzheimer's Disease Genetics Consortium (ADGC); The Alzheimer's Disease Sequencing Project (ADSP); Cuccaro, Michael L.; Cruchaga, Carlos; Pericak-Vance, Margaret A.; Farrer, Lindsay A.; Wang, Li-San; Schellenberg, Gerard D.; Mayeux, Richard P.; Haines, Jonathan L.; Jefferson, Angela L.; Kukull, Walter A.; Keene, C. Dirk; Saykin, Andrew J.; Thompson, Paul M.; Martin, Eden R.; Bennett, David A.; Barnes, Lisa L.; Schneider, Julie A.; Crane, Paul K.; Hohman, Timothy J.; Dumitrescu, Logan; Radiology and Imaging Sciences, School of Medicine
    Background: 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.