Archer, Derek B.Eissman, Jaclyn M.Mukherjee, ShubhabrataLee, Michael L.Choi, Seo-EunScollard, PhoebeTrittschuh, 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)Alzheimer's Disease Sequencing Project (ADSP)Cuccaro, Michael L.Pericak-Vance, Margaret A.Farrer, Lindsay A.Wang, Li-SanSchellenberg, Gerard D.Mayeux, Richard P.Haines, Jonathan L.Jefferson, Angela L.Kukull, Walter A.Keene, C. DirkSaykin, Andrew J.Thompson, Paul M.Martin, Eden R.Bennett, David A.Barnes, Lisa L.Schneider, Julie A.Crane, Paul K.Dumitrescu, LoganHohman, Timothy J.2024-06-172024-06-172024Archer DB, Eissman JM, Mukherjee S, et al. Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease. Alzheimers Dement. 2024;20(2):1268-1283. doi:10.1002/alz.13508https://hdl.handle.net/1805/41577Introduction: Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline. Methods: We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts. Results: We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non-Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene-level analysis, we found novel genes for memory decline on chromosomes 1 (SLC25A44), 11 (BSX), and 15 (DPP8). Memory performance and memory decline shared genetic architecture with AD-related traits, neuropsychiatric traits, and autoimmune traits. Discussion: We discovered several novel loci, genes, and genetic correlations associated with late-life memory performance and decline. Highlights: Late-life memory has high heritability that is similar across ancestries. We discovered four novel variants associated with late-life memory. We identified four novel genes associated with late-life memory. Late-life memory shares genetic architecture with psychiatric/autoimmune traits.en-USAttribution-NonCommercial 4.0 InternationalAlzheimer's diseaseGWASGeneticsMemoryArticle