Science: Nearly 300 units work together to reveal the role of genes in the cortex.

Learn about the latest progress in neuroscience ● click the blue word to pay attention to us ● the human cerebral cortex is a high-level center, accounting for about half of the whole brain volume. In addition to its large size, the types of neurons are diverse, which lays the structural foundation for its complex functions, such as attention, perception, language, imagination, reasoning, movement, etc.the cortical surface is highly expanded and curled, forming many grooves and fissures. During the development of cortex, the surface area of cortex increases nearly 1000 times, but its thickness does not increase equivalently.the radiation unit hypothesis holds that the increase of cortical surface area is caused by neural progenitor cells, and its thickness is determined by the number of nerve source divisions.the average thickness of adult cortex is 2-3cm. The decrease of thickness often leads to the decrease of intelligence and cognitive ability.current studies have shown that regional or global changes in cortical surface area and thickness are closely related to neuropsychiatric disorders.March 20, 2020, Sarah E Medland research team leads a total of 297 research teams around the world, including the Institute of brain intelligence science and technology of Fudan University, and published an article in science magazine, which for the first time revealed the role of genes in human cortical tissue structure, which laid the foundation for further research on cortical function.the team conducted a genome-wide meta-analysis using the brain magnetic resonance imaging data of 51665 people in 60 research groups. The cortex was divided into 34 regions by brain atlas, and the effects of genes on the structure of cerebral cortex such as surface area and average thickness were analyzed.a total of 306 loci were found in 22 pairs of autosomes (118 of which were not previously found to be related to cortical structure), and the number of gene loci on chromosomes 2, 3, 5, 6, 14 and 15 was relatively large.after multiple correction, only 199 alleles were significant, including 187 influencing surface area and 12 influencing thickness.on the whole, the common variations of these genes can account for 34% of the changes in the surface area of the cortex and 26% of the changes in the average thickness of the cortex. That is to say, among all the factors affecting the changes in the surface area and average thickness of the whole cortex, the common variations of the genes can determine 34% and 26% respectively, which is still a large proportion and has a great impact on the structure of the cortex.it was further found that there was a negative genetic correlation between cortical surface area and mean thickness, which indicated that genetic factors had opposite effects on surface area and thickness.more specifically, the genetic factors that have the strongest influence on the surface area and thickness mainly focus on the gene activity regulation sequence (promoter and enhancer sequence), while the genes related to fetal metaphase can significantly affect the vocal changes of cortical surface area, while the significant changes of average thickness are the regulation sites of gene activity related to adulthood, which are opposite to each other It is consistent with the radiation unit hypothesis.signal pathway analysis showed that there were 92 genes related to total cortical surface area, mainly chromatin binding related genes, and only 4 genes were associated with mean thickness.from each sub area of the cortex, there is also a negative genetic correlation between the cortical surface area and the average thickness, that is to say, the gene changes of a certain sub region cause the surface area to increase, but at the same time, it will reduce the thickness.in addition, in terms of physical distance, there is a positive genetic correlation between the adjacent brain regions, while there is a negative genetic correlation between the proximal and distal cortical regions. This phenomenon also occurs in the mean thickness.multivariate GWAS analysis showed that 902 genes were associated with cortical surface area, and the classic Wnt signaling pathway was the most abundant.from the disease point of view, there is a positive genetic correlation between total cortical surface area and Parkinson's disease, but there is no causal evidence.in addition, allelic mutations can increase the risk of depression, insomnia, attention deficit hyperactivity disorder and other diseases.in conclusion, we found gene loci related to cortical surface area and average thickness through bioinformatics, which provided clues for further study on the role of genes on cortical structure.References: the genetic architecture of the human cervical cortex