| Application: | 16066, Genetics of brain asymmetry and language-related disorders |
| Title: | Large-Scale Phenomic and Genomic Analysis of Brain Asymmetrical Skew |
| Size: | 4.5 MB |
| Archived: | 30 Sep 2021 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
Return 3917
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Notes
The human cerebral hemispheres show a left right asymmetrical torque pattern, which has been claimed to be absent in chimpanzees. The functional significance and developmental mechanisms are unknown. We carried out the largest-ever phenomic and genomic analysis of global brain shape asymmetry in MRI data. At the population level, there was an anterior and dorsal skew of the right hemisphere, relative to the left. Both skews were associated independently with handedness, and various regional gray and white matter metrics oppositely in the two hemispheres, as well as other variables related to cognitive functions, sociodemographic factors, and physical and mental health. The two skews showed SNP-based heritabilities of 4~13%, but also substantial polygenicity in causal mixture model analysis, and no individually significant loci were found in GWAS for either skew. There was evidence for a significant genetic correlation between horizontal brain skew and autism. These results provide new insights into biological and other factors which associate with human brain asymmetry.Application 16066
Genetics of brain asymmetry and language-related disorders
Left-right asymmetry is an important feature of the human brain. One prominently asymmetric brain network underlies the uniquely human ability to speak and understand language. A lack of brain asymmetry is associated with variation in human cognitive abilities linked to language, and also susceptibility to cognitive disorders including language impairment and dyslexia. The genetic basis of human brain asymmetry is unknown, while links between asymmetric anatomy and function are poorly understood. It is likely that genes involved in brain asymmetry contain variants in the population that influence cognitive performance and cognitive disorders. We will test whether certain genetic profiles affect asymmetric brain structure and function particularly for regions involved in speaking and listening. We will also test whether these same genetic variations affect susceptibility to language-related disorders including dyslexia and Specific Language Impairment. Both can be severe disorders with lifelong impacts on achievement and mental health. Dyslexia is identified as a disability in the UK's Equality Act 2010. According to the British Dyslexia Association, roughly 4% of the population has severely impaired reading ability. Each illiterate pupil, by age 37, is estimated to cost taxpayers an extra roughly 50,000GBP. Some brain regions are asymmetrical and important for speech and language. We will use Biobank brain imaging data in combination with genetic data to identify genomic profiles linked to the thickness, surface area and volumes of these regions. If possible, we will also do a similar analysis with Biobank MRI data that measures how active the language regions are during rest. We will follow up the findings in other cohorts of people with brain imaging and genetic data, and language-related disorders and genetic data. We are leading members of scientific consortia that study these questions with meta-analysis. Data will be used from all Biobank participants who have done MRI scans (roughly 5000 at the time of writing, September 2015). We will also need the genotype data of as many of these participants as possible. The larger the available dataset, the more statistical power there is to detect and measure the individual and pooled effects of genomic variants on brain anatomy and function.
| Lead investigator: | Dr Clyde Francks |
| Lead institution: | Max Planck Institute for Psycholinguistics |
4 related Returns
| Return ID | App ID | Description | Archive Date |
|---|---|---|---|
| 3651 | 16066 | A large-scale population study of early life factors influencing left-handedness | 14 Jul 2021 |
| 3633 | 16066 | Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment | 9 Jul 2021 |
| 4001 | 16066 | Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization | 14 Oct 2021 |
| 4002 | 16066 | The genetic architecture of structural left™right asymmetry of the human brain | 14 Oct 2021 |
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