Genome‐wide investigation of a neuropathological cohort offers novel insights in the genetic risk underlying hallmark and co‐morbid lesions implicated in Alzheimer’s disease
Implementing phenotypic information on neuropathological lesions in a hypothesis-free genome-wide investigation as a preliminary screening rendered genome-wide significant and suggestive loci which can contribute to a deeper understanding of the individual lesions observed in AD. From our preliminary results we observe the benefits of accurate phenotyping on GWAS power. Despite small sample size, we managed to detect genome-wide significant associations for AD-related lesions by eliminating phenotypic heterogeneity. Associated loci will be subjected to gene prioritization and functional validation analysis to determine the causal risk genes. For more commonly investigated hallmark lesions, replication analysis will be performed in publicly available cohorts.
Authors
- Alicja Ronisz (ORCID: https://orcid.org/0000-0002-4310-0445)
- Philip Van Damme (ORCID: https://orcid.org/0000-0002-4010-2357)
- Klara Gawor (ORCID: https://orcid.org/0000-0001-7571-5420)
- Kristel Sleegers (ORCID: https://orcid.org/0000-0002-0283-2332)
- Dietmar Rudolf Thal (ORCID: https://orcid.org/0000-0002-1036-1075)
- Marta J. Koper (ORCID: https://orcid.org/0000-0003-2255-6088)
- Fahri Küçükali (ORCID: https://orcid.org/0000-0002-3835-9639)
- Markus Otto (ORCID: https://orcid.org/0000-0003-4273-4267)
- Rik R. Vandenberghe (ORCID: https://orcid.org/0000-0001-6237-2502)
- Christine A. F. Von Arnim (ORCID: https://orcid.org/0000-0002-8614-2223)
- Jasper Van Dongen (ORCID: https://orcid.org/0000-0001-5599-0046)
- Celeste Laureyssen (ORCID: https://orcid.org/0000-0002-7373-2099)
Institutions
- University of Antwerp (BE)
- Universitair Ziekenhuis Leuven (BE)
- Universitätsmedizin Göttingen (DE)
- VIB-UAntwerp Center for Molecular Neurology (BE)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- University Hospital Ulm (DE)
- KU Leuven (BE)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/alz.092254
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00