Biology subjects

Postema, M. C.

Publications and source records attributed to Postema, M. C..

5 recordsLinked to original sources

bioRxiv2023

Imaging genetics of language network functional connectivity reveals links with language-related abilities, dyslexia and handedness

Language is supported by a distributed network of brain regions with a particular contribution from the left hemisphere. A multi-level understanding of this network requires studying its genetic architecture. We used resting-state imaging data from 29,681 participants (UK Biobank) to measure connectivity between 18 left-hemisphere regions involved in multimodal sentence-level processing, as well as their right-hemisphere homotopes, and interhemispheric connections. Multivariate genome-wide association analysis of this total network, based on genetic variants with population frequencies > 1%, identified 14 genomic loci, of which three were also associated with asymmetry of intrahemispheric connectivity. Polygenic dispositions to lower language-related abilities, dyslexia and left-handedness were associated with generally reduced leftward asymmetry of functional connectivity. Exome-wide association analysis based on rare, protein-altering variants (frequencies[≤] 1%) suggested 7 additional genes. These findings shed new light on genetic contributions to language network organization and related behavioural traits.

genomics↗

bioRxiv2020

Analysis of structural brain asymmetries in Attention-Deficit/Hyperactivity Disorder in 39 datasets

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here we performed the largest-ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,978 people with ADHD and unaffected 1,917 controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modelling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t=2.4, P=0.019). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t=2.4, P=0.007) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohens d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

neuroscience↗

bioRxiv2019

Handedness and Other Variables Associated with Human Brain Asymmetrical Skew

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. Here we carried out the largest-ever analysis of global brain shape asymmetry in magnetic resonance imaging data. Three population datasets were used, the UK Biobank (N = 39,678), Human Connectome Project (N = 1,113) and BIL&GIN (N = 453). 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 grey 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 (rg=-0.40, p=0.0075) between horizontal brain skew and Autism Spectrum Disorder. These results provide the first large-scale description of population-average brain skews and their inter-individual variations, their replicable associations with handedness, and insights into biological and other factors which associate with human brain asymmetry.

neuroscience↗

bioRxiv2019

Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium

BackgroundLeft-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power.\n\nMethodsWe investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.\n\nResultsASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohens d = 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.\n\nConclusionAltered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.

neuroscience↗

bioRxiv2018

The genetics of situs inversus totalis without primary ciliary dyskinesia

Situs inversus totalis (SIT), a complete left-right mirror reversal of the visceral organs, is usually described as a recessive disorder. SIT can occur with Primary Ciliary Dyskinesia (PCD). However, most people with SIT do not have PCD, and the etiology of their condition remains poorly studied. Those without PCD may have an elevated rate of left-handedness, implying developmental mechanisms linking brain and body laterality. We sequenced the genomes of 15 people with SIT, of which six had PCD, and 15 controls. The SIT subjects with PCD all had likely recessive mutations in genes already known to cause PCD. Two non-PCD SIT cases also had recessive mutations in known PCD genes, suggesting reduced penetrance for PCD in some SIT cases. One non-PCD SIT case had a recessive mutation in PKD1L1, which has previously been linked to SIT without PCD. However, six of the nine non-PCD SIT cases, including most of the left-handers in this dataset, had no obvious candidate genes or significant pathways affected by the mutations that they carried. While we cannot exclude a monogenic basis, more complex genetic models must also be considered, as well as environmental influences or random effects in early development.

genetics↗