Journal Article

DZNE-2023-00591

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic risk factor clustering within and across neurodegenerative diseases.

Koretsky, M. J. ; Alvarado, C. ; Makarious, M. B. ; Vitale, D. ; Levine, K. ; Bandres-Ciga, S. ; Dadu, A. ; Scholz, S. W. ; Sargent, L. ; Faghri, F. ; Iwaki, H. ; Blauwendraat, C.Extern* ; Singleton, A. ; Nalls, M. ; Leonard, H. L. (Last author)DZNE*

2023
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awad161

Abstract: Overlapping symptoms and co-pathologies are common in closely related neurodegenerative diseases (NDDs). Investigating genetic risk variants across these NDDs can give further insight into disease manifestations. In this study we have leveraged genome-wide single nucleotide polymorphisms and genome-wide association study summary statistics to cluster patients based on their genetic status across identified risk variants for five NDDs (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Lewy body dementia and frontotemporal dementia). The multi-disease and disease-specific clustering results presented here provide evidence that NDDs have more overlapping genetic aetiology than previously expected and how neurodegeneration should be viewed as a spectrum of symptomology. These clustering analyses also show potential subsets of patients with these diseases that are significantly depleted for any known common genetic risk factors suggesting environmental or other factors at work. Establishing that NDDs with overlapping pathologies share genetic risk loci, future research into how these variants might have different effects on downstream protein expression, pathology and NDD manifestation in general is important for refining and treating NDDs.

Keyword(s): Humans (MeSH) ; Neurodegenerative Diseases: genetics (MeSH) ; Genome-Wide Association Study (MeSH) ; Parkinson Disease: genetics (MeSH) ; Lewy Body Disease: genetics (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Risk Factors (MeSH) ; dementia ; genome-wide association study ; machine learning ; single-nucleotide polymorphism ; unsupervised

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Contributing Institute(s):

1. Core ICRU (Core ICRU)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

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Database coverage:
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