Genetic correlation and gene-based pleiotropy analysis for four major neurodegenerative diseases with summary statistics.
Neurobiol Aging
; 124: 117-128, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36740554
ABSTRACT
Recent genome-wide association studies suggested shared genetic components between neurodegenerative diseases. However, pleiotropic association patterns among them remain poorly understood. We here analyzed 4 major neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), and found suggestively positive genetic correlation. We next implemented a gene-centric pleiotropy analysis with a powerful method called PLACO and detected 280 pleiotropic associations (226 unique genes) with these diseases. Functional analyses demonstrated that these genes were enriched in the pancreas, liver, heart, blood, brain, and muscle tissues; and that 42 pleiotropic genes exhibited drug-gene interactions with 341 drugs. Using Mendelian randomization, we discovered that AD and PD can increase the risk of developing ALS, and that AD and ALS can also increase the risk of developing FTD, respectively. Overall, this study provides in-depth insights into shared genetic components and causal relationship among the 4 major neurodegenerative diseases, indicating genetic overlap and causality commonly drive their co-occurrence. It also has important implications on the etiology understanding, drug development and therapeutic targets for neurodegenerative diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Doenças Neurodegenerativas
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Doença de Pick
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Demência Frontotemporal
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Doença de Alzheimer
/
Esclerose Lateral Amiotrófica
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China