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Biobank-scale characterization of Alzheimer’s disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers… — Europe PMC PPR:PPR935217

Source: Europe PMC
Original: https://europepmc.org/article/PPR/PPR935217
DOI: 10.1101/2024.11.03.24313587
License (as archived): CC0-1.0
Archived: 2026-10-06T15:12:42.167Z
SHA-256 of the archived text: ce4c892ad26b413c169b5d707a49568fae5e2f8bc2c5c13d416f99e6a4a67990
Stable URL of this page: https://metraipolis.com/documento/dc_e36ed16489ea

How to cite

Biobank-scale characterization of Alzheimer’s disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers… — Europe PMC PPR:PPR935217 — Europe PMC, https://europepmc.org/article/PPR/PPR935217 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_e36ed16489ea (Metraipolis archive dc_e36ed16489ea, sha256 ce4c892ad26b413c169b5d707a49568fae5e2f8bc2c5c13d416f99e6a4a67990)

BibTeX

@misc{dce36ed16489ea,
  title = {Biobank-scale characterization of Alzheimer’s disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers… — Europe PMC PPR:PPR935217},
  howpublished = {Europe PMC},
  url = {https://europepmc.org/article/PPR/PPR935217},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_e36ed16489ea; sha256 ce4c892ad26b413c169b5d707a49568fae5e2f8bc2c5c13d416f99e6a4a67990},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC, https://europepmc.org/article/PPR/PPR935217. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

Alzheimer’s disease and related dementias (AD/ADRDs) pose a significant global public health challenge, underscored by the intricate interplay of genetic and environmental factors that differ across ancestries. To effectively implement equitable, personalized therapeutic interventions on a global scale, it is essential to identify disease-causing mutations and genetic risk and resilience factors across diverse ancestral backgrounds. Exploring genetic-phenotypic correlations across the globe enhances the generalizability of research findings, contributing to a more inclusive and universal understanding of disease. This study leveraged biobank-scale data to conduct the largest multi-ancestry whole-genome sequencing characterization of AD/ADRDs. We aimed to build a valuable catalog of potential disease-causing, genetic risk and resilience variants impacting the etiology of these conditions. We thoroughly characterized genetic variants from key genes associated with AD/ADRDs across 11 genetic ancestries, utilizing data from All of Us, UK Biobank, 100,000 Genomes Project, Alzheimer’s Disease Sequencing Project, and the Accelerating Medicines Partnership in Parkinson’s Disease, including a total of 25,001 cases and 93,542 controls. We prioritized 116 variants possibly linked to disease, including 18 known pathogenic and 98 novel variants. We detected previously described disease-causing variants among controls, leading us to question their pathogenicity. Notably, we showed a higher frequency of APOE ε4/ε4 carriers among individuals of African and African Admixed ancestry compared to other ancestries, confirming ancestry-driven modulation of APOE -associated AD/ADRDs. A thorough assessment of APOE revealed a disease-modifying effect conferred by the TOMM40 rs11556505, APOE rs449647, 19q13.31 rs10423769, NOCT rs13116075, CASS4 rs6024870, and LRRC37A rs2732703 variants among APOE ε4 carriers across different ancestries. In summary, we compiled the most extensive catalog of established and novel genetic variants in known genes increasing risk or conferring resistance to AD/ADRDs across diverse ancestries, providing clinical insights into their genetic-phenotypic correlations. The findings from this investigation hold significant implications for potential clinical trials and therapeutic interventions on a global scale. Finally, we present an accessible and user-friendly platform for the AD/ADRDs research community to help inform and support basic, translational, and clinical research on these debilitating conditions ( https://niacard.shinyapps.io/MAMBARD_browser/ ).

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: medRxiv, 2024 (prima pubblicazione 2024-11-04).
Identificativi: DOI 10.1101/2024.11.03.24313587.
Pagina: https://europepmc.org/article/PPR/PPR935217 — https://doi.org/10.1101/2024.11.03.24313587. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-10-06T15:11:36.246Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.