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Insights into cortical organisation and neurodevelopment from a genome wide association study (GWAS) of 2,347 structural cortical phenotypes

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If you have a question about this talk, please contact John Mollon.

The host for this talk is Simon Baron-Cohen (sb205@cam.ac.uk)

Abstract. Our understanding of the genetic architecture of the development of the human cerebral cortex is limited both in terms of the diversity of brain structural phenotypes and the anatomical granularity of their associations with genetic variants. Here, we conducted genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging (MRI)-derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,843 individuals. These phenotypes include cortical thickness, surface area, grey matter volume, and measures of folding, neurite density, and water diffusion. We identified 4,353 experiment-wide significant loci across all genome-wide association studies (GWAS). We demonsted varying levels of pleiotropy among the 13 phenotypes and across the 180 bilateral cortical regions. Multiple lines of analyses identified distinct genetic latent structures and causal relationships among the phenotypes, partly relating to different underlying developmental and cellular mechanisms. We also identified differential enrichment for human-specific evolutionary signatures, and neurodevelopmental and constrained genes across the 13 phenotypes. Finally, we identified complex inter-phenotype and inter-regional genetic relationships among the 13 phenotypes which reflect developmental differences among these phenotypes. These analyses provide unprecedented granular insights into the development, evolution, and genetic organisation of the human cortex

This talk is part of the Zangwill Club series.

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