Biology subjects

de Zubicaray, G. I.

Publications and source records attributed to de Zubicaray, G. I..

8 recordsLinked to original sources

bioRxiv2025

Genetic and environmental contributions to ReHo and fALFF in early adolescence vary across brain regions

Research on genetic and environmental influences on brain function generally focuses on connections between brain areas. A different yet unexplored approach is to examine activity within local brain regions. We investigated the influence of genes and environmental effects on two specific measures of local brain function: Regional Homogeneity (ReHo) and fractional Amplitude of Low-Frequency Fluctuations (fALFF). Participants were drawn from a sample of adolescent twins on two occasions (mean ages 11.5 and 13.2 years, N = 278 and 248). Results showed that genetic and environmental factors influenced brain function in almost all 210 cortical regions examined. Moreover, genetic and common environmental factors influencing ReHo and fALFF values at wave 1 (9-14 years) also influenced values at wave 2 (10-16 years) for many regions. However, the influence of genetic and common environmental factors varied across the cortex, exhibiting different patterns in different regions. Furthermore, we found new (i.e., independent) genetic and environmental influences on brain activity at wave 2, again with regional patterns. Exploratory analyses found weak associations between anxiety and depressive symptoms and local brain function in several regions of the temporal lobe. These findings are consistent with similar studies of other resting-state functional MRI metrics (i.e., functional connectivity).

neuroscience↗

bioRxiv2024

Reference curves for harmonizing multi-site regional diffusion MRI metrics across the lifespan

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data and used to assess the effect of the ApoE4 risk factor for dementia in WM across the lifespan. We found significant associations between ApoE4 and FA in WM regions associated with neurodegenerative disease even in healthy individuals across the lifespan, with regional age-by-genotype interactions. Our lifespan reference curves and tools to harmonize new dMRI data to the curves are publicly available as eHarmonize (https://github.com/ahzhu/eharmonize).

neuroscience↗

bioRxiv2023

Normative Modeling of Brain Morphometry Across the Lifespan using CentileBrain: Algorithm Benchmarking and Model Optimization

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins, and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3,000 study participants. The model and scripts described here are freely available through CentileBrain (https://centilebrain.org/).

bioinformatics↗

bioRxiv2022

The Queensland Twin Adolescent Brain Project, a longitudinal study of adolescent brain development

We describe the Queensland Twin Adolescent Brain (QTAB) dataset and provide a detailed methodology and technical validation to facilitate data usage. The QTAB dataset comprises multimodal neuroimaging, as well as cognitive and mental health data collected in adolescent twins over two sessions (session 1: N = 422, age 9-14 years; session 2: N = 304, 10-16 years). The MRI protocol consisted of T1-weighted (MP2RAGE), T2-weighted, FLAIR, high-resolution TSE, SWI, resting-state fMRI, DWI, and ASL scans. Two fMRI tasks were added in session 2: an emotional conflict task and a passive movie-watching task. Outside of the scanner, we assessed cognitive function using standardised tests. We also obtained self-reports of symptoms for anxiety and depression, perceived stress, sleepiness, pubertal development measures, and risk and protective factors. We additionally collected several biological samples for genomic and metagenomic analysis. The QTAB project was established to promote health-related research in adolescence.

neuroscience↗

bioRxiv2022

Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages

Mechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 individuals, aged 4-89 years) depended on cell-specific marker gene expression levels. We found differences amidst early-life (<20 years), mid-life (20-60 years), and late-life (>60 years) in the patterns of association between inter-regional profiles of cortical thickness and expression profiles of marker genes for CA1 and S1 pyramidal cells, astrocytes, and microglia. Gene ontology and enrichment analyses indicated that each of the three life-stages was associated with different biological processes and cellular components: synaptic modeling in early life, neurotransmission in mid-life, and neurodegeneration in late-life. These findings provide mechanistic insights into age-related cortical thinning during typical development and aging.

neuroscience↗

bioRxiv2019

The reliability and heritability of cortical folds and their genetic correlations across hemispheres.

The structure of the brains cortical folds varies considerably in human populations. Specific patterns of cortical variation arise with development and aging, and cortical traits are partially influenced by genetic factors. The degree to which genetic factors affect cortical folding patterning remains unknown, yet may be estimated with large-scale in-vivo brain MRI. Using multiple MRI datasets from around the world, we estimated the reliability and heritability of sulcal morphometric characteristics including length, depth, width, and surface area, for 61 sulci per hemisphere of the human brain. Reliability was assessed across four distinct test-retest datasets. We meta-analyzed the heritability across three independent family-based cohorts (N > 3,000), and one cohort of largely unrelated individuals (N~9,000) to examine the robustness of our findings. Reliability was high (interquartile range for ICC: 0.65-0.85) for sulcal metrics. Most sulcal measures were moderately to highly heritable (heritability estimates = 0.3-0.7). These genetic influences vary regionally, with the earlier forming sulci having higher heritability estimates. The central sulcus, the subcallosal and the collateral fissure were the most highly heritable regions. For some frontal and temporal sulci, left and right genetic influences did not completely overlap, suggesting some lateralization of genetic effects on the cortex.

genetics↗

bioRxiv2018

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3,337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc) -three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. CpG sites associated with hippocampus volume were significantly enriched within cancer-related genes and within regulatory elements containing the transcriptionally repressive histone H3K27 tri-methylation mark that is vital for stem cell fate specification. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

genomics↗

bioRxiv2018

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet we know little about the specific genetic loci influencing human cortical structure. To identify genetic variants, including structural variants, impacting cortical structure, we conducted a genome-wide association meta-analysis of brain MRI data from 51,662 individuals. We analysed the surface area and average thickness of the whole cortex and 34 regions with known functional specialisations. We identified 255 nominally significant loci (P [≤] 5 x 10-8); 199 survived multiple testing correction (P [≤] 8.3 x 10-10; 187 surface area; 12 thickness). We found significant enrichment for loci influencing total surface area within regulatory elements active during prenatal cortical development, supporting the radial unit hypothesis. Loci impacting regional surface area cluster near genes in Wnt signalling pathways, known to influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinsons disease, insomnia, depression and ADHD.\n\nOne Sentence SummaryCommon genetic variation is associated with inter-individual variation in the structure of the human cortex, both globally and within specific regions, and is shared with genetic risk factors for some neuropsychiatric disorders.

genetics↗