Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization...

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Childhood neurodevelopmental disorders like autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) cause significant disability.
• Biomarkers for these conditions and drug targets remain limited.
• This study explores causal links between plasma proteins and ASD, ADHD, and TS.

Purpose of the Study:

• To investigate the causal effects of plasma proteins on the risk of ASD, ADHD, and TS.
• To identify potential plasma protein biomarkers for these neurodevelopmental disorders.
• To explore novel therapeutic targets through proteomic analysis.

Main Methods:

• Utilized a two-sample Mendelian Randomization (MR) approach.
• Analyzed genome-wide association data for ASD, ADHD, and TS against 2994 plasma proteins.
• Employed inverse-variance weighted, MR-Egger, and weighted median methods for robust analysis and sensitivity testing.

Main Results:

• Elevated MAPKAPK3 and MRPL33 protein levels were causally associated with increased ASD risk.
• Increased MANBA protein levels were causally linked to a reduced risk of ADHD.
• No significant plasma protein risk factors were identified for Tourette syndrome (TS).

Conclusions:

• Findings suggest the MAPK/ERK signaling pathway and mitochondrial dysfunction are implicated in ASD pathogenesis.
• A deficiency in beta-mannosidase may contribute to the development of ADHD.
• Plasma proteomic analysis offers insights into the biological mechanisms underlying neurodevelopmental disorders.