Association and shared biological bases between birth weight and cortical structure.

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Associations between birth weight and cortical structure are known but not fully understood.
• The underlying biological mechanisms linking early growth to brain development require further elucidation.

Purpose of the Study:

• To investigate the associations between birth weight and cortical structural phenotypes.
• To identify shared genetic, proteomic, and cellular bases for these associations.

Main Methods:

• Genome-wide association studies (GWAS) and Mendelian randomization (MR) analyses were employed.
• Transcriptome-wide association study (TWAS), proteome-wide association study (PWAS), and summary-based MR (SMR) were used to identify shared genes and proteins.
• Cell-type expression-specific integration for complex traits (CELLECT) analysis explored enriched cell types.

Main Results:

• MR confirmed positive associations between birth weight and global cortical folding, local gyrification, surface area, and volume.
• TWAS/SMR identified three genes (CNNM2, RABGAP1, CENPW) and PWAS/SMR identified four proteins (CNNM2, RAB7L1, RAB5B, PPA2) linked to both birth weight and cortical structure.
• CELLECT analysis highlighted pericytes, GABAergic neurons, and cerebrovascular cells as enriched cell types for birth weight.

Conclusions:

• Early life growth significantly influences cortical structure.
• Shared transcriptomic, proteomic, and cellular pathways underpin the relationship between birth weight and brain development.
• Identified genes and cell types offer potential targets for future research into cortical development mechanisms.