Genetic insights into human cortical organization and development through genome-wide analyses of 2,347 neuroimaging phenotypes.
Nat Genet
; 55(9): 1483-1493, 2023 09.
Article
in En
| MEDLINE
| ID: mdl-37592024
ABSTRACT
Our understanding of the genetics of the human cerebral cortex is limited both in terms of the diversity and the anatomical granularity of brain structural phenotypes. Here we conducted a genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging-derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,663 individuals and identified 4,349 experiment-wide significant loci. These phenotypes include cortical thickness, surface area, gray matter volume, measures of folding, neurite density and water diffusion. We identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with cortical expansion are associated with cephalic disorders. Finally, we identified complex interphenotype and inter-regional genetic relationships among the 13 phenotypes, reflecting the developmental differences among them. Together, these analyses identify distinct genetic organizational principles of the cortex and their correlates with neurodevelopment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cerebral Cortex
/
Genome-Wide Association Study
Type of study:
Systematic_reviews
Limits:
Humans
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2023
Document type:
Article
Affiliation country: