Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease.
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Archer Derek B, Eissman Jaclyn M, 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), Alzheimer's Disease Sequencing Project (ADSP), Cuccaro Michael L, 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, Dumitrescu Logan, Hohman Timothy J
Аннотация
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.