Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease
Derek B Archer1,2, Jaclyn M Eissman1,2, Shubhabrata Mukherjee3
1Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Introduction:
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.
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