scholarly journals The genetic architecture of structural left–right asymmetry of the human brain

Author(s):  
Zhiqiang Sha ◽  
Dick Schijven ◽  
Amaia Carrion-Castillo ◽  
Marc Joliot ◽  
Bernard Mazoyer ◽  
...  

AbstractLeft–right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and it can be altered in cognitive and psychiatric disorders. No mechanism has yet been identified for establishing the human brain’s left–right axis. We performed multivariate genome-wide association scanning of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci associated with different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left–right axis determination in other organs of invertebrates and frogs. Genetic variants associated with brain asymmetry overlapped with those associated with autism, educational attainment and schizophrenia. Comparably large datasets will likely be required in future studies, to replicate and further clarify the associations of microtubule-related genes with variation in brain asymmetry, behavioural and psychiatric traits.

Author(s):  
Zhiqiang Sha ◽  
Dick Schijven ◽  
Amaia Carrion-Castillo ◽  
Marc Joliot ◽  
Bernard Mazoyer ◽  
...  

Left-right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and can be altered in cognitive and psychiatric disorders1-8. No mechanism has yet been identified for establishing the human brain’s left-right axis9. We performed multivariate genome-wide association scanning (mvGWAS) of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci affecting different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left-right axis determination in other organs of invertebrates and frogs10-12. Genetic variants affecting brain asymmetry overlapped with those influencing autism, educational attainment and schizophrenia.


2021 ◽  
Author(s):  
Zhiqiang Sha ◽  
Dick Schijven ◽  
Clyde Francks

AbstractAutism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing versus empathizing cognitive styles, with resemblances to male versus female average sex differences. Left-right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes, and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores (PRS) for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness and subcortical volume measures in 32,256 participants from the UK Biobank. PRS for the two disorders were positively correlated (r=0.08, p=7.13×10−50), and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each PRS was associated with multivariate brain asymmetry after adjusting for sex, ASD PRS r=0.03, p=2.17×10−9, schizophrenia PRS r=0.04, p=2.61×10−11, but the multivariate patterns were mostly distinct for the two PRS, and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both PRS were associated with asymmetries of regions important for language and executive functions, consistent with behavioural associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risk for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.


Open Medicine ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Zlatislav Stoyanov ◽  
Lyoubka Decheva ◽  
Irina Pashalieva ◽  
Piareta Nikolova

AbstractThe principle of symmetry-asymmetry is widely presented in the structural and functional organization of the nonliving and living nature. One of the most complex manifestations of this principle is the left-right asymmetry of the human brain. The present review summarizes previous and contemporary literary data regarding the role of brain asymmetry in neuroimmunomodulation. Some handedness-related peculiarities are outlined additionally. Brain asymmetry is considered to be imprinted in the formation and regulation of the individual’s responses and relationships at an immunological level with the external and internal environment. The assumptions that the hemispheres modulate immune response in an asymmetric manner have been confirmed in experiments on animals. Some authors assume that the right hemisphere plays an indirect role in neuroimmunomodulation, controlling and suppressing the left hemispheric inductive signals.


2020 ◽  
Author(s):  
Ada Admin ◽  
Yann C. Klimentidis ◽  
Amit Arora ◽  
Michelle Newell ◽  
Jin Zhou ◽  
...  

Although hyperlipidemia is traditionally considered a risk factor for type-2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL-C increases T2D risk. We thus sought to more comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that levels of circulating LDL-C were negatively associated with T2D prevalence (OR=0.41[0.39, 0.43] per mmol/L unit of LDL-C), despite positive associations of circulating LDL-C with HbA1c and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower circulating LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank (n=431,167) and the GLGC consortium (n=188,577), and T2D from the DIAGRAM consortium (n=898,130). We identified 31 loci associated with lower circulating LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this dual phenotype, and 9 have previously been implicated in non-alcoholic fatty liver disease. These findings extend our current understanding of the higher T2D risk among individuals with low circulating LDL-C, and of the underlying mechanisms, including those responsible for the diabetogenic effect of LDL-C-lowering medications.


2021 ◽  
Author(s):  
Ángel Ferrero-Serrano ◽  
Sarah M Assmann

Plants respond to environmental fluctuations through plastic phenotypic shifts. Whether a plastic response upon environmental variability is adaptive or not has been subject to debate. Using a set of Iberian Arabidopsis accessions, we quantified an interplay between passive plastic reductions in leaf areas that we found typical of accessions from productive environments and homeostatic leaf areas responses to drought typified by accessions originating from unproductive environments. Results from Genome-Wide Association Studies (GWAS) and Transcriptome Wide Association Studies (TWAS) highlight the role of auxin-related processes and, in particular, the possible role of the SMALL AUXIN UP RNA 26 (SAUR26) gene in the regulation of the observed plastic responses. Homeostatic responses in leaf area potential following drought were typical of accessions with lower leaf area potential under well-watered conditions. Transcripts that were negatively associated with leaf area potential and positively associated with homeostatic and positive leaf area plasticity following drought showed functional enrichment in ion transport processes. We hypothesized that the contrasting plastic and homeostatic responses in leaf area potential were associated with differential intrinsic water use efficiency (WUEi). We confirmed this relationship in a metanalysis conducted using previously published δ13C measurements. Our results highlight the adaptive role of homeostatic leaf area response to water depletion arising from increased WUEi. The concerted utilization of Genome-Wide Association Studies (GWAS), Transcriptome Wide Association Studies (TWAS), and expression Genome-Wide Association Studies (eGWAS) allows integration of phenotype, genotype, and transcript abundance to identify both "plasticity genes" and "homeostasis genes" associated with drought stress responses.


2010 ◽  
Vol 9 (2) ◽  
pp. 181-192 ◽  
Author(s):  
Jenny Phillimore ◽  
Lisa Goodson

Britain has entered a new era of super-diversity and many regions of the UK are experiencing the arrival of new communities. Refugee Community Organisations (RCOs) have developed following the arrival of new asylum seeking and refugee communities, and have been charged with the role of supporting the integration of these newcomers. However, there is much evidence to suggest that they are functioning only with individuals rather than working with institutions to transform systems and ensure welfare provision is adapted to account for diverse needs. This paper looks at the role of RCOs in attempting transformation and, using data collected through survey, interviews, and participatory action research, examines the extent to which RCOs are able to engage with the public and wider voluntary sector, to ensure that refugees' welfare needs can be met. It finds that in addition to the much-researched functional barriers to transformation, there are major institutional barriers to engagement. Institutions have failed to adapt their systems to enable representation of new communities instead expecting RCOs to build their own capacity to communicate. The paper ends by offering some ideas around resourcing RCOs to be represented and developing the capacity of institutions to adapt to new diversity.


Author(s):  
Zhiqiang Sha ◽  
Dick Schijven ◽  
Clyde Francks

AbstractAutism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing vs. empathizing cognitive styles, with resemblances to male vs. female average sex differences. Left–right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness, and subcortical volume measures in 32,256 participants from the UK Biobank. Polygenic risks for the two disorders were positively correlated (r = 0.08, p = 7.13 × 10−50) and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each polygenic risk score was associated with multivariate brain asymmetry after adjusting for sex, ASD r = 0.03, p = 2.17 × 10−9, and schizophrenia r = 0.04, p = 2.61 × 10−11, but the multivariate patterns were mostly distinct for the two polygenic risks and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both polygenic risks were associated with asymmetries of regions important for language and executive functions, consistent with behavioral associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risks for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.


2012 ◽  
Vol 219 ◽  
pp. R77-R89 ◽  
Author(s):  
Justin van de Ven

The National Employment Savings Trust (NEST) is a new pension scheme that will be introduced for employees on modest incomes in the UK from 2012. This paper draws out the implications of the NEST, focusing upon low-paid employees and their employers using data from the Annual Survey of Hours and Earnings. The results suggest that the NEST will increase labour costs by between 0.6 and 0.8 per cent on average, and have a disproportionate effect on low pay industries and private sector firms employing fewer than 25 employees. The analysis highlights the potential role of the minimum wage to shield low pay workers from paying a share of the subsidies that the NEST will afford to its members.


2017 ◽  
Author(s):  
Brian Boutwell ◽  
David Hinds ◽  
Jorim Tielbeek ◽  
Ken K. Ong ◽  
Felix R. Day ◽  
...  

AbstractProgress identifying the genetic determinants of personality has historically been slow, with candidate gene studies and small-scale genome-wide association studies yielding few reproducible results. In the UK Biobank study, genetic variants in CADM2 and MSRA were recently shown to influence risk taking behavior and irritability respectively, representing some of the first genomic loci to be associated with aspects of personality. We extend this observation by performing a personality “phenome-scan” across 16 traits in up to 140,487 participants from 23andMe for these two genes. Heritability estimates for these traits ranged from 5-19%, with both CADM2 and MSRA demonstrating significant effects on multiple personality types. These associations covered all aspects of the big five personality domains, including specific facet traits such as compliance, altruism, anxiety and activity / energy. This study both confirms and extends the original observations, highlighting the role of genetics in aspects of mental health and behavior.


2019 ◽  
Vol 21 (2) ◽  
pp. 255-275 ◽  
Author(s):  
Charlotte Grynberg ◽  
Stefanie Walter ◽  
Fabio Wasserfallen

A surprising development in the post-referendum Brexit process has been that vote intentions have remained largely stable, despite the cumbersome withdrawal negotiations. We examine this puzzle by analyzing the role of voters’ expectations about the European Union’s willingness to accommodate the UK after the pro-Brexit vote. Using data from the British Election Study, we explore how these expectations are updated over time, and how they are related to vote intentions. We find that voters who were more optimistic about the European Union’s response were more likely to vote Leave. Over the course of the negotiations, Leavers have become more disillusioned. These adjustments, however, have not translated into shifts in vote intentions. Overall, we find evidence that motivated reasoning is an important driver of public opinion on Brexit.


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