Análisis de aleatorización mendeliana basado en datos de neuroimagen cerebral y datos resumidos revela el impacto del...

Área de la Ciencia:

• Genetics; Neuroscience; Aging Research

Sus antecedentes:

• Schizophrenia (SZ) presents with significant non-neurological comorbidities, suggesting systemic aging involvement beyond accelerated brain aging.
• The biological mechanisms connecting multisystem aging and schizophrenia remain largely unexplored.

Objetivo del estudio:

• To investigate the tissue-specific genetic links between aging-related genes and schizophrenia (SZ) risk.
• To identify potential aging pathways implicated in SZ development.
• To explore the relationship between key aging genes and brain predicted age difference (PAD) in SZ patients.

Principales métodos:

• Utilized genome-wide association study (GWAS) data for SZ-associated SNPs, aging gene datasets, and GTEx cis-eQTL data.
• Employed tissue-specific Mendelian randomization (MR) and summary data-based MR (SMR) to analyze gene expression and SZ risk.
• Conducted enrichment analyses to identify aging pathways and correlated gene expression with brain PAD in clinical patients.

Principales resultados:

• Identified tissue-specific aging genes, including SNCA, ACE, BRCA1, MLH1, VEGFA, MAPT, and ARMS2, potentially influencing SZ.
• Tissue-specific cis-eQTLs were found to impact SZ risk through aging pathways.
• Elevated BRCA1 expression was significantly associated with a higher brain predicted age difference (PAD) in schizophrenia patients.

Conclusiones:

• This research offers crucial insights into the connection between schizophrenia and multisystem aging.
• The findings enhance the understanding of specific tissue-aging genes contributing to schizophrenia risk.