Genetic Variation Underlying Traumatic Brain Injury (TBI) and Late Onset Alzheimer's Disease (LOAD)
Abstract
We previously computed episodic memory trajectories in 13,979 ethnically diverse elderly(ages 72 to 85 years) with two to 15 years of follow-up, and with known dementia status, age, education and APOE genotypes at baseline. Adjusted trajectories of episodic memory performance over time were estimated using Latent Class Mixed Models. In this reporting cycle, we aimed to identify common and rare genetic variation that may be responsible for uncharacterized genetic risk underlying individual differences in longitudinal performance on memory. We included the UK Biobank dataset to the analysis cohorts, which increased our sample size to 24,769 individuals. The Latent Class Mixed Model was used to derive episodic memory trajectories within each of the study cohorts. The slope of residualized episodicmemory scores was used as outcome in an APOE stratified (non-APOE stratified, APOE_4 andAPOE_non4 subsamples) genome=wide gene-based analyses. Association results from each study cohort within each subsample were meta-analyzed. Consistent with previous studies, the majority of the study participants maintain their memory performance over time (ranging from51% to 98%). The strongest association signal for the episodic memory trajectories (p=4.8 x10-8) was achieved at chromosomal region 6p22 among in the APOE_non4 subsample. Meta-analysis results in the non-APOE stratified and APOE_4 subsamples also yielded several chromosomal regions associated with memory performance over time, although significance level was diminished (p~ 10-6). Identifying genes associated with progression of episodic memory performance over time in older adulthood provides the possibility of identifying at-risk population subgroups that can benefit from possible interventions to enhance cognitive function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1097579
Entities
People
- Badri N. Vardarajan
- Sandra Barral
Organizations
- Columbia University