Biology subjects

Colombo, M.

Publications and source records attributed to Colombo, M..

At least 19 recordsLinked to original sources

bioRxiv2025

Asymmetric induction of IL-23R by CpG and IL-15 in proliferative CLL fractions highlights intraclonal heterogeneity in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is sustained by complex interactions with the microenvironment, which provides signals for leukemic cell survival and proliferation. Among these, cytokines of the IL-12 family have emerged as relevant regulators of immune responses and tumor biology, yet their contribution to CLL remains incompletely defined. Previous studies showed that CLL cells can acquire responsiveness to IL-23 after T cell-dependent stimulation with CD40L, raising the question of whether T cell-independent signals can similarly induce functional receptor expression. Here we investigated the effect of CpG oligodeoxynucleotides, alone or in combination with interleukin-15 (IL-15), on IL-12 family receptor expression in CLL cells. We found that CpG + IL-15 stimulation significantly increased IL-23R and IL-12R{beta}1 expression, while IL-12R{beta}2 remained largely unresponsive. As a consequence, the complete IL-23 receptor complex was robustly induced, whereas IL-12 receptor assembly was only marginally enhanced. This skewing toward IL-23 rather than IL-12 signaling suggests that innate immune stimuli preferentially promote pathways supporting inflammation and survival, while limiting tumor-suppressive IL-12 responsiveness. Analysis of intraclonal heterogeneity revealed an asymmetric distribution of IL-23R among CXCR4/CD5-defined subfractions: the proliferative fraction, representing recently divided cells, expressed higher levels of IL-23R compared to the resting fraction. These findings suggest that IL-23 responsiveness is particularly enriched in the proliferating compartment of the leukemic clone. Overall, our results indicate that CpG and IL-15 stimulation drive a selective expansion of IL-23 signaling capacity in CLL, with preferential engagement of proliferative subfractions. This imbalance between IL-23 activation and insufficient IL-12R{beta}2 induction may represent a critical pathogenic mechanism and a potential therapeutic target.

cancer biology↗

bioRxiv2025

Transcranial magnetic vs intracranial electric stimulation: a direct comparison of their effects via scalp EEG recordings

BackgroundSingle-pulse Transcranial Magnetic Stimulation (TMS) and Intracranial Electrical Stimulation (IES) are widely used to probe cortical excitability and connectivity, but their electrophysiological effects have never been compared. ObjectiveThis study aims to fill this gap by using high-density scalp electroencephalogram (hd-EEG) as a common read-out to compare human brain responses to TMS and IES. MethodsThe dataset includes TMS-evoked potentials (TEPs) acquired from healthy subjects (n=22) and IES-evoked potentials (IEPs) recorded from drug-resistant epileptic patients (n=31) during wakefulness. In a subset of subjects TEPs (n=12) and IEPs (n=13) were also recorded during NREM sleep. Amplitude, spectral, and spatiotemporal features of TMS and IES responses, as well as their estimated electrical fields, were compared. ResultsWe observed marked differences between TMS and IES responses. During wakefulness, IEPs are considerably larger, slower and associated with a suppression of cortical activity, whereas TEPs are characterized by multiple waves of recurrent activation. These differences are attenuated during NREM, during which both TMS and IES elicit large EEG responses associated with a prominent suppression of cortical activity. At the global level, the spatiotemporal complexity of the responses to both TMS and IES decreases consistently following the transition from wakefulness to NREM sleep. ConclusionDespite the limitations due to different subject populations (healthy vs pathological), our findings provide a first reference to parallel non-invasive and invasive brain stimulation and to interpret their differential effects. They also offer important insight on how cortical responsiveness is shaped by inhibition and adaptation mechanisms depending on input parameters and brain states. Highlights- IES evokes higher signal-to-noise EEG responses than TMS. - IES responses are larger, slower, and lead to cortical suppression. - TMS elicits faster recurrent waves, with no suppression during wakefulness. - Both TMS and IES converge to similar patterns during NREM sleep.

neuroscience↗

bioRxiv2025

Genomic insights into the virulence repertoire and hemibiotrophic lifestyle of the grapevine black rot pathogen Phyllosticta ampelicida

Phyllosticta ampelicida, the causal agent of grapevine black rot, is a globally emerging pathogen that infects all grapevine green tissues, with young shoots and berries being particularly susceptible. Severe infections can result in total crop loss. To investigate its virulence repertoire, we generated a high-quality genome assembly of strain GW18.1 using long-read sequencing, resulting in 22 scaffolds, including four complete chromosomes and 12 chromosome arms, with a total genome size of 35.6 Mb and 10,289 predicted protein-coding genes. Two additional strains (TN2 and LB22.1) were sequenced with short reads to assess intraspecies diversity. Comparative genomics revealed a conserved virulence factor repertoire, including 314 carbohydrate-active enzymes (CAZymes), 17 cytochrome P450s, 35 peroxidases, and 20 secondary metabolite biosynthetic gene clusters (BGCs). Trophic lifestyle prediction based on gene content supports a biotrophic-like lifestyle consistent with hemibiotrophic pathogens. Broader comparisons with other Phyllosticta species and ten plant-pathogenic fungi pointed to species-specific features, while analysis of gene family evolution identified expansions and contractions in transporters and CAZymes. These genomic resources will support efforts to better understand and manage grapevine black rot.

genomics↗

bioRxiv2025

A Two-Phase Fluid Structure Interaction Model of Mucociliary Clearance Driven by Cilium

This study introduces a two-phase fluid-structure interaction (FSI) model of mucociliary clearance (MCC), utilizing direct cilia modeling and non-Newtonian Carreu rheology for the mucus layer (ML). A novel method for prescribing cilia beat patterns (CBP) was developed, enabling realistic motion replication by imposing displacement at specific cilium points. Computational simulations evaluated MCC performance by comparing rheological properties and assessing the interaction between the ML and periciliary layer (PCL). Results highlight improved ML-PCL coupling and enhanced mucus transport using non-Newtonian ML. This approach enables deeper insights into mucus dynamics and the role of cilia motion in MCC.

bioengineering↗

bioRxiv2025

Aortic annuloplasty FSI digital twin of 3D-printed phantoms with 4D-flow MRI comparison

BackgroundAortic annuloplasty, involving the implantation of an external ring around the aortic root to reduce annular dimensions, is a promising treatment for aortic valve insufficiency. However, its hemodynamic effects remain underexplored due to the absence of computational models validated by experimental and clinical data. MethodsThis study introduces a computational fluid-structure interaction (FSI) model of supra valvular aortic annuloplasty using 4D-flow magnetic resonance imaging (MRI). Native and post-annuloplasty conditions of idealized aortic root phantoms, including the aortic valve, were CAD-modelled and 3D-printed with elastic resin. These phantoms were tested in a mock circulatory flow-loop providing normal pulsatile physiologic conditions using a glycerol-water mixture to simulate blood viscosity. Flow and pressure data collected from sensors were used as boundary conditions for FSI simulations. Experimental velocity fields from 4D-flow MRI were compared to computational results to assess model accuracy. ResultsMRI scans of the annuloplasty model showed an increased peak systolic velocity (up to 145.4 cm/s) and localized flow alterations, corresponding to a higher pressure gradient across the valve. During regurgitation, the annuloplasty model showed broader velocity distributions compared to the native condition. The FSI simulations closely matched 4D-flow MRI data, with strong correlation coefficients (r > 0.93) and minimal Bland-Altman differences, particularly during systolic phases. ConclusionsThis study establishes an integrative methodology combining in-vitro, in-silico, and clinical imaging techniques to evaluate aortic annuloplasty hemodynamics. The validated digital twin framework offers a pathway for patient-specific modelling, enabling prediction of surgical outcomes and optimization of aortic valve repair strategies.

bioengineering↗

bioRxiv2025

Dual-targeting strategy to repurpose Cetuximab with HFn nanoconjugates for immunotherapy of triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly aggressive and treatment-resistant malignancy, characterized by the lack of targeted therapies and poor clinical outcomes. Here, we present a dual-targeting strategy combining the anti-EGFR monoclonal antibody Cetuximab (CTX) with H-ferritin (HFn), a nanoparticle targeting transferrin receptor 1 (TfR1), for potential immunotherapy in CTX-resistant tumors. The HFn-CTX nanoconjugate exhibited favorable biophysical properties, including a hydrodynamic size of <30 nm, and significantly enhanced antibody-dependent cellular cytotoxicity (ADCC) in TNBC spheroids compared to CTX alone. Conversely, glioblastoma spheroids did not exhibit comparable reactivity. This effect correlated with elevated cell-surface EGFR expression and plasma-membrane lingering of the nanoconjugate in TNBC cells, facilitating robust immune activation. Biodistribution studies showed selective accumulation of the HFn-CTX nanoconjugate in TNBC tumors in vivo. These findings highlight the potential of HFn-CTX nanoconjugates to repurpose CTX for refractory cancers that express EGFR at high levels like TNBC, leveraging dual-receptor targeting to amplify immune-mediated cytotoxicity and overcome resistance.

biochemistry↗

bioRxiv2024

Variant-to-function dissection of rare non-coding GWAS loci with high impact on blood traits

Understanding the function of genetic variants associated with human traits and diseases remains a significant challenge. Here we combined analyses based on natural genetic variation and genetic engineering to dissect the function of 94 non-coding variants associated with haematological traits. We describe 22 genetic variants impacting haematological variation through gene expression. Further, through in-depth functional analysis, we illustrate how a rare, non-coding variant near the CUX1 transcription factor impacts megakaryopoiesis through modulation of the CUX1 transcriptional cascade. Collectively, our findings enhance the functional interpretation of genetic association studies and advance understanding of how non-coding variants contribute to blood and immune system variation.

genetics↗

bioRxiv2024

Non-Human Recognition of Orthography: How is it implemented and how does it differ from Human orthographic processing

The ability to robustly recognize strings of letters, a cornerstone of reading, was observed in baboons and pigeons despite their lack of phonological and semantic knowledge. Here, we apply a comparative modeling approach to investigate the neuro-cognitive basis of orthographic decision behavior in humans, baboons, and pigeons, addressing whether phylogenetic relatedness entails similar underlying neuro-cognitive phenotypes. We use the highly transparent SpeechLess Reader (SLR) model, which assumes letter-string recognition based on a computational implementation of predictive coding, whereby orthographic decisions rely on prediction-error signals emerging from multiple representational levels: visual-pixel, letter, and letter-sequence representations. We investigate which representations species use during successful orthographic decision-making. We introduce multiple SLR variants, each including one or more prediction-error representations, and compare the simulations of each variant with orthographic decisions from individuals of three species after learning letter strings without meaning. Humans predominantly relied on letter-sequence-level representations, resulting in the highest task performance in behavior and model simulations. Baboons also relied on sequence-based representations, but in combination with pixel- and letter-level representations. In contrast, pigeons relied more on pixel and letter-level representations. These findings suggest that the orthographic representations used in orthographic decisions reflect phylogenetic distance: Humans and baboons use more similar representations than pigeons. Overall, the description of orthographic decisions based on a small set of representations and computations was highly successful in describing behavior, even for humans who mastered reading in its entirety.

animal behavior and cognition↗

bioRxiv2023

Viscoelastic Deformability Cytometry: Ultra-high Throughput Platform for Mechanical Phenotyping of Cells in Liquid and Solid Biopsies

Due to the differences in mechanical properties between cancer cells and their benign counterparts, the mechanical characteristics of cells have emerged as a significant feature in diagnosing cancer. Consequently, measuring cell deformability as a means of mechanical phenotyping is promising for both the detection and classification of the disease. However, performing high-throughput single-cell deformability measurements on liquid or solid tissue biopsies remains a significant challenge within a clinical setting. Herein, we introduce an ultra-high throughput viscoelastic-based microfluidic platform to measure the cell mechanical properties at rates of up to 100,000 cells/s. Thanks to the viscoelastic property of the fluid, cells are focused and deformed within the same platform obviating the need for any sheath fluid. We used the presented platform for cell phenotyping in both liquid and solid tumor biopsies, such as identification of malignant lymphocytes in peripheral blood samples and glioblastoma-type cell classification from solid tumor samples. The presented platform has the potential to open new opportunities in the assessment of cancer, enable precise mechanical profiling of rare cells, and facilitate sensitive diagnostic applications.

bioengineering↗

bioRxiv2023

The first report on the use of a zona pellucida binding assay to compare the effects of European bison (Bison bonasus) epididymal spermatozoa cryopreservation in two different extenders

The wisent (or European bison) Bison bonasus is a species that has gone through a bottleneck, resulting in a narrow gene pool of the current population. Presently, the protection program for this species, in addition to protecting the habitat, is aimed at preserving gene pool. One of its elements is creating a bank of gametes with the intention of using them in constantly developed Assisted Reproductive Techniques in this species. In order to use the potential of the gametes stored in the bank as effectively as possible, it is extremely important to assess their post-freezing quality. Wisent epididymal spermatozoa stored in the bank are evaluated using basic semen analysis methods, the CASA system and flow cytometry. So far, functional tests of spermatozoa have not been introduced to the evaluation protocol of spermatozoa obtained post mortem from European bison. This article, for the first time describes the use of the zona pellucida binding test to assess the quality of cryopreserved wisent epididymal spermatozoa. Due to the close relationship between the species, the Zona binding Assay protocol developed for cattle was used. To exclude the influence of the composition of the extender used for cryopreservation, the spermatozoa were cryopreserved in the Extender based on Tris buffer, egg yolk and glycerol and in the commercial extender Andromed(R). Regardless of the diluent used, 100% of the oocytes had sperm attached. The average number of spermatozoa attached to the oocyte was 66.26 for the Tris-based diluent group and 27.37 for the Andromed(R) - frozen group. The advantage of the Tris based extender resulted from ZBA seems to coincide with the results of the basic and advanced semen evaluation. The conducted experiment showed that the ZBA protocol developed for cattle is suitable for the evaluation of wisent epididymal spermatozoa.

zoology↗

bioRxiv2023

A pro-inflammatory stem cell niche drives myelofibrosis through a targetable galectin 1 axis

Myeloproliferative neoplasms are stem cell-driven cancers associated with a large burden of morbidity and mortality. The majority of patients present with early-stage disease, but a substantial proportion progress to myelofibrosis and/or secondary leukemia, advanced cancers with a poor prognosis and high symptom burden. Currently, it remains difficult to predict progression, and we lack therapies that reliably prevent or reverse fibrosis development. A major bottleneck to the discovery of disease-modifying therapies has been an incomplete understanding of the interplay between perturbed cellular and molecular states. Several cell types have individually been implicated, but a comprehensive analysis of myelofibrotic bone marrow is lacking. We therefore mapped the crosstalk between bone marrow cell types in myelofibrotic bone marrow. We found that inflammation and fibrosis are orchestrated by a quartet of immune and stromal cell lineages - with basophils and mast cells creating a TNF signaling hub, communicating with megakaryocytes, mesenchymal stromal cells and pro-inflammatory fibroblasts. We identified the y-galactoside binding protein galectin 1 as a striking biomarker of progression to myelofibrosis and poor survival in multiple patient cohorts, and as a promising therapeutic target, with reduced myeloproliferation and fibrosis in vitro and in vivo and improved survival following galectin 1 inhibition. In human bone marrow organoids, TNF increased galectin 1 expression, suggesting a feedback loop wherein the pro-inflammatory MPN clone creates a self-reinforcing niche, fueling progression to advanced disease. This study provides a valuable resource for studying hematopoietic cell-niche interactions, with broad relevance for cancer-associated inflammation and disorders of tissue fibrosis.

cancer biology↗

bioRxiv2023

Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells

Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA degradation pathway that targets for degradation faulty mRNAs with premature termination codons as well as many physiological mRNAs encoding full-length proteins. Consequently, NMD functions in both, quality control and post-transcriptional regulation of gene expression, and it has been implicated in the modulation of cancer progression. To investigate the role of NMD in cancer, we knocked out SMG7 in the HT1080 human fibrosarcoma cell line. SMG7 is involved in deadenylation-coupled exonucleolytic mRNA decay, one of the two main degradation pathways in mammalian NMD. Genome-wide proteomic and transcriptomic analyses confirmed that NMD is severely compromised in these SMG7-knockout HT1080 cells. We compared the oncogenic properties between the parental, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. In parallel, we tested the effect of a drug inhibiting the NMD factor SMG1 on the HT1080 cells to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays as well as a mouse xenograft tumor model, we show that the oncogenic properties of the parental HT1080 cells are severely compromised when NMD is inhibited. Molecular pathway analysis revealed a strong reduction of the matrix metalloprotease 9 (MMP9) gene expression in NMD-suppressed cells. Since MMP9 expression promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation in NMD-suppressed cells explains, at least partially, their reduced tumorigenicity. Collectively, our findings emphasize the therapeutic potential of NMD inhibition for the treatment of certain types of cancer. SignificanceNonsense-mediated mRNA decay (NMD) is a eukaryotic RNA decay pathway with reported roles in regulating cellular stress responses, differentiation, and viral defense. NMD has also emerged as a modulator of cancer progression, however, the available evidence supports both, a tumor suppressor as well as a pro-tumorigenic role for NMD. We discovered that NMD inhibition results in impaired tumorigenicity in the HT1080 human fibrosarcoma cell line and uncovered a direct correlation between NMD activity and the expression levels the pro-tumorigenic gene MMP9. Restoring MMP9 expression in NMD-suppressed cells partially improved their oncogenic properties. These results show that the tumorigenicity of the HT1080 fibrosarcoma cells relies on NMD activity and highlights the potential use of NMD inhibition as a therapeutic approach.

molecular biology↗

bioRxiv2022

The cancer-associated RBM39 bridges the pre-mRNA, U1 and U2 snRNPs to regulate alternative splicing

Pharmacologic depletion of RNA-binding motif 39 (RBM39) using aryl sulfonamides represents a promising anti-cancer therapy. However, its efficiency correlates with the expression level of DCAF15 which acts at the interface between RBM39, the drug and the E3-ubiquitin ligase. Consequently, the identification of alternative approaches to deplete RBM39 independently of DCAF15 is required. Here, we combined transcriptomic analysis, functional assays, and structural biology to elucidate the molecular mechanisms governing RBM39 homeostasis. Our data revealed that RBM39 autoregulates the splicing of its own pre-mRNA by triggering the inclusion of a poison exon. During this process, RBM39 selects the 3-splice site of the toxic exon, helps the recruitment of U1 snRNP on its weak 5-splice site and bridges the 3-splice site recognition machinery. The elucidation of the molecular mechanisms controlling RBM39 homeostasis provides unprecedented insights into alternative 3-splice site selection and a solid frame to design alternative anti-cancer therapies.

molecular biology↗

bioRxiv2022

Human bone marrow organoids for disease modelling, discovery and validation of therapeutic targets in hematological malignancies

A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from iPSCs committed to mesenchymal, endothelial and hematopoietic lineages. These 3-dimensional structures capture key features of human bone marrow - stroma, lumen-forming sinusoidal vessels and myeloid cells including pro-platelet forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGF{beta} stimulation and engraftment with myelofibrosis but not healthy donor-derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow-like milieu. This enabling technology is likely to accelerate discovery and prioritization of novel targets for bone marrow disorders and blood cancers. Significance StatementWe present a 3D, vascularised human bone marrow organoid that supports growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment, and provides a much-needed, ex vivo tool for prioritization of new therapeutics.

cancer biology↗

bioRxiv2021

EEG spectral exponent as a synthetic index for the longitudinal assessment of stroke recovery.

BackgroundQuantitative EEG (qEEG) can capture changes in brain activity that follow a stroke. Accordingly, EEG metrics could be used to monitor patients state and recovery. Although qEEG metrics traditionally focus on oscillatory activity, recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological brain states. ObjectiveTo assess neurophysiological impairment and recovery from mono-hemispheric stroke by means of the Spectral Exponent (SE), a metric that reflects EEG slowing and quantifies the power-law decay of the EEG Power Spectral Density (PSD). To relate neurophysiological recovery with patients functional outcome. MethodsEighteen patients (n=18) with Middle Cerebral Artery (MCA) ischaemic stroke were retrospectively enrolled for this study. Patients underwent EEG recording in the sub-acute phase (T0) and after 2 months of physical rehabilitation (T1). Sixteen healthy controls (HC; n=16) matched by age and sex were enrolled as a normative group. SE values and narrow-band PSD were estimated for each recording. We compared SE and band-power between patients and HC, and between the affected (AH) and unaffected hemisphere (UH) at T0 and T1 in patients. ResultsAt T0, stroke patients showed significantly more negative SE values than HC (p=0.003), reflecting broad-band EEG slowing. Moreover, SE over the AH was consistently more negative compared to the UH and showed a renormalization at T1 in our patient sample. This SE renormalization significantly correlated with NIHSS improvement (R= 0.63, p=0.005). ConclusionsSE is a reliable readout of the electric changes occurring in the brain after an ischaemic cortical lesion. Moreover, SE holds the promise to be a robust method to assess stroke impairment as well as to monitor and predict functional outcome.

neuroscience↗

bioRxiv2020

Extracellular vesicles from human adipose stem cells are neuroprotective after stroke in rats

Ischemic stroke is a prominent cause of death and disability, demanding innovative therapeutic strategies. Accordingly, extracellular vesicles (EVs) released from mesenchymal stem cells are promising tools for stroke treatment. In this study, we evaluated the potential neuroprotective properties of EVs released from human adipose tissue stem cells (hAT-MSC), which were obtained from a healthy individual submitted to liposuction. A single intranasal EVs administration was performed 24 h after the ischemic stroke in rats. The EVs brain penetration and the tropism to brain zone of ischemia was observed 18 h after administration. Thus, we measured EVs neuroprotection against the ischemic stroke-induced impairment on long-term motor and behavioral performance. Indeed, one single intranasal EVs administration reversed the stroke damages on: i) front paws symmetry; ii) working memory, short- and long-term memory; iii) anxiety-like behavior. These findings highlight hAT-MSC-derived EVs as a promising therapeutic strategy in stroke.

biochemistry↗

bioRxiv2019

GUN1 influences the accumulation of NEP-dependent transcripts and chloroplast protein import in Arabidopsis cotyledons upon perturbation of chloroplast protein homeostasis

Correct chloroplast development and function require coordinated expression of chloroplast and nuclear genes. This is achieved through chloroplast signals that modulate nuclear gene expression in accordance with the chloroplasts needs. Genetic evidence indicates that GUN1, a chloroplast-localized pentatricopeptide-repeat (PPR) protein with a C-terminal Small MutS-Related (SMR) domain, is involved in integrating multiple developmental and stress-related signals in both young seedlings and adult leaves. Recently, GUN1 was found to interact physically with factors involved in chloroplast protein homeostasis, and with enzymes of tetrapyrrole biosynthesis in adult leaves that function in various retrograde signaling pathways. Here we show that, following perturbation of chloroplast protein homeostasis i) by growth in lincomycin-containing medium, or ii) in mutants defective in either the FtsH protease complex (ftsh), plastid ribosome activity (prps21-1 and prpl11-1) or plastid protein import and folding (cphsp70-1), GUN1 influences NEP-dependent transcript accumulation during cotyledon greening and also intervenes in chloroplast protein import.

plant biology↗

bioRxiv2019

Expression quantitative trait loci-derived scores and white matter microstructure in UK Biobank: a novel approach to integrating genetics and neuroimaging

BackgroundExpression quantitative trait loci (eQTL) are genetic variants associated with gene expression. Using genome-wide genotype data, it is now possible to impute gene expression using eQTL mapping efforts. This approach can be used to analyse previously unexplored relationships between gene expression and heritable in vivo measures of human brain structural connectivity.\n\nMethodsUsing large-scale eQTL mapping studies, we computed 6,457 gene expression scores (eQTL scores) using genome-wide genotype data in UK Biobank, where each score represents a genetic proxy measure of gene expression. These scores were then tested for associations with two diffusion tensor imaging measures, fractional anisotropy (NFA=14,518) and mean diffusivity (NMD=14,485), representing white matter structural integrity.\n\nResultsWe found FDR-corrected significant associations between 8 eQTL scores and structural connectivity phenotypes, including global and regional measures ({beta}absolute FA=0.0339-0.0453; MD=0.0308-0.0381) and individual tracts ({beta}absolute FA=0.0320-0.0561; MD=0.0295-0.0480). The loci within these eQTL scores have been reported to regulate expression of genes involved in various brain-related processes and disorders, such as neurite outgrowth and Parkinsons disease (DCAKD, SLC35A4, SEC14L4, SRA1, NMT1, CPNE1, PLEKHM1, UBE3C).\n\nDiscussionOur findings indicate that eQTL scores are associated with measures of in vivo brain connectivity and provide novel information not previously found by conventional genome-wide association studies. Although the role of expression of these genes regarding white matter microstructural integrity is not yet clear, these findings suggest it may be possible, in future, to map potential trait- and disease-associated eQTL to in vivo brain connectivity and better understand the mechanisms of psychiatric disorders and brain traits, and their associated imaging findings.

bioinformatics↗