Cerebrospinal and Brain Proteins Implicated in Neuropsychiatric and Risk Factor Traits: Evidence from Mendelian Randomization.

ABSTRACT: Neuropsychiatric disorders present a global health challenge, necessitating an understanding of their molecular mechanisms for therapeutic development. Using Mendelian randomization (MR) analysis, this study explored associations between genetically predicted levels of 173 proteins in cerebrospinal fluid (CSF) and 25 in the brain with 14 neuropsychiatric disorders and risk factors. Follow-up analyses assessed consistency across plasma protein levels and gene expression in various brain regions. Proteins were instrumented using tissue-specific genetic variants, and colocalization analysis confirmed unbiased gene variants. Consistent MR and colocalization evidence revealed that lower cortical expression of low-density lipoprotein receptor-related protein 8, coupled higher abundance in the CS

SUBMITTER: de La Harpe R 

PROVIDER: S-EPMC10886978 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature