| Title: | Biobank-scale genetic characterization of Alzheimer's disease and related dementias across diverse ancestries |
| Journal: | Nature Communications |
| Published: | 14 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40813364/ |
| DOI: | https://doi.org/10.1038/s41467-025-62108-y |
Publication 16560
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Abstract
Alzheimer's disease and related dementias (AD/ADRDs) pose a significant global public health challenge. To effectively implement personalized therapeutic interventions on a global scale, it is essential to identify disease-causing, risk, and resilience factors across diverse ancestral backgrounds. This study leveraged biobank-scale data to conduct a large multi-ancestry whole-genome sequencing characterization of AD/ADRDs. We thoroughly explored the role of protein-coding and splicing variants from key genes associated with AD/ADRDs across 11 ancestries, utilizing data from five distinct biobanks, including a total of 25,001 cases and 93,542 controls. We compiled the most extensive catalog of known and novel genetic variation in AD/ADRDs in a global context, providing clinical insights into their genetic-phenotypic correlations. A thorough assessment of APOE revealed ancestry-driven modulation of APOE-associated AD/ADRDs, as well as disease-modifying effects conferred by several variants among APOE ε4 carriers. Finally, we present an accessible and user-friendly platform to support future ADRD research (https://niacard.shinyapps.io/MAMBARD_browser/).</p>
12 Keywords
- Aged
- Alzheimer Disease
- Apolipoprotein E4
- Apolipoproteins E
- Biological Specimen Banks
- Dementia
- Female
- Genetic Predisposition to Disease
- Genetic Variation
- Humans
- Male
- Whole Genome Sequencing
15 Authors
- Marzieh Khani
- Fulya Akçimen
- Spencer M. Grant
- Suleyman Can Akerman
- Paul Suhwan Lee
- Faraz Faghri
- Hampton Leonard
- Jonggeol Jeffrey Kim
- Mary B. Makarious
- Mathew J. Koretsky
- Jeffrey D. Rothstein
- Cornelis Blauwendraat
- Mike A. Nalls
- Andrew Singleton
- Sara Bandres-Ciga
1 Application
| Application ID | Title |
|---|---|
| 33601 | Dissecting the genetic architecture of neurodegenerative diseases |
Enabling scientific discoveries that improve human health