| Title: | Integration of GWAS and brain transcriptomic analyses in a multiethnic sample of 35,245 older adults identifies DCDC2 gene as predictor of episodic memory maintenance |
| Journal: | Alzheimer's & Dementia |
| Published: | 7 Dec 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34873813/ |
| DOI: | https://doi.org/10.1002/alz.12524 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170841 |
| Citations: | 5 (4 in last 2 years) as of 8 Aug 2024 |
Publication 12648
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Abstract
Identifying genes underlying memory function will help characterize cognitively resilient and high-risk declining subpopulations contributing to precision medicine strategies. We estimated episodic memory trajectories in 35,245 ethnically diverse older adults representing eight independent cohorts. We conducted apolipoprotein E (APOE)-stratified genome-wide association study (GWAS) analyses and combined individual cohorts' results via meta-analysis. Three independent transcriptomics datasets were used to further interpret GWAS signals. We identified DCDC2 gene significantly associated with episodic memory (Pmeta = 3.3 x 10-8 ) among non-carriers of APOE ε4 (N = 24,941). Brain transcriptomics revealed an association between episodic memory maintenance and (1) increased dorsolateral prefrontal cortex DCDC2 expression (P = 3.8 x 10-4 ) and (2) lower burden of pathological Alzheimer's disease (AD) hallmarks (paired helical fragment tau P = .003, and amyloid beta load P = .008). Additional transcriptomics results comparing AD and cognitively healthy brain samples showed a downregulation of DCDC2 levels in superior temporal gyrus (P = .007) and inferior frontal gyrus (P = .013). Our work identified DCDC2 gene as a novel predictor of memory maintenance.</p>
11 Keywords
- Aged
- Alzheimer Disease
- Amyloid beta-Peptides
- Apolipoprotein E4
- Apolipoproteins E
- Brain
- Genome-Wide Association Study
- Humans
- Memory, Episodic
- Microtubule-Associated Proteins
- Transcriptome
15 Authors
- Yizhe Gao
- Daniel Felsky
- Dolly Reyes-Dumeyer
- Sanjeev Sariya
- Miguel Arce Rentería
- Yiyi Ma
- Hans-Ulrich Klein
- Stephanie Cosentino
- Philip L. De Jager
- David A. Bennett
- Adam M. Brickman
- Gerard D. Schellenberg
- Richard Mayeux
- Sandra Barral
- UKBB CHAP
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