Genetic risk factor clustering within and across neurodegenerative diseases.
Brain
; 146(11): 4486-4494, 2023 11 02.
Article
de En
| MEDLINE
| ID: mdl-37192343
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladie de Parkinson
/
Maladies neurodégénératives
/
Maladie à corps de Lewy
/
Maladie d'Alzheimer
Type d'étude:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Humans
Langue:
En
Journal:
Brain
Année:
2023
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique