Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases.
Journal
NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390
Informations de publication
Date de publication:
28 Apr 2023
28 Apr 2023
Historique:
received:
16
03
2023
accepted:
27
03
2023
medline:
29
4
2023
pubmed:
29
4
2023
entrez:
28
4
2023
Statut:
epublish
Résumé
Genetic correlation ([Formula: see text]) between traits can offer valuable insight into underlying shared biological mechanisms. Neurodegenerative diseases overlap neuropathologically and often manifest comorbid neuropsychiatric symptoms. However, global [Formula: see text] analyses show minimal [Formula: see text] among neurodegenerative and neuropsychiatric diseases. Importantly, local [Formula: see text] s can exist in the absence of global relationships. To investigate this possibility, we applied LAVA, a tool for local [Formula: see text] analysis, to genome-wide association studies of 3 neurodegenerative diseases (Alzheimer's disease, Lewy body dementia and Parkinson's disease) and 3 neuropsychiatric disorders (bipolar disorder, major depressive disorder and schizophrenia). We identified several local [Formula: see text] s missed in global analyses, including between (i) all 3 neurodegenerative diseases and schizophrenia and (ii) Alzheimer's and Parkinson's disease. For those local [Formula: see text] s identified in genomic regions containing disease-implicated genes, such as SNCA, CLU and APOE, incorporation of expression quantitative trait loci identified genes that may drive genetic overlaps between diseases. Collectively, we demonstrate that complex genetic relationships exist among neurodegenerative and neuropsychiatric diseases, highlighting putative pleiotropic genomic regions and genes. These findings imply sharing of pathogenic processes and the potential existence of common therapeutic targets.
Identifiants
pubmed: 37117178
doi: 10.1038/s41531-023-00504-1
pii: 10.1038/s41531-023-00504-1
pmc: PMC10147945
doi:
Types de publication
Journal Article
Langues
eng
Pagination
70Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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