Biology subjects

Gandal, M. J.

Publications and source records attributed to Gandal, M. J..

At least 19 recordsLinked to original sources

bioRxiv2026

Autism genes converge on three functional programs organized by neuronal subclass, developmental timing, and cortical patterning

Our companion sequencing study uncovered 253 genes robustly associated with autism spectrum disorder (ASD), yet the biological programs they impact, and the cellular, developmental, and spatial contexts in which they converge, remain unresolved. Here we systematically contextualize genes associated with ASD across neurodevelopment and cortical areas, integrating developmental single-cell and spatial atlases with gene- and isoform co-expression, regulatory, proteomic, and synaptic networks. Genetic burden concentrates within temporally-resolved neuronal subclasses: newborn excitatory neurons, immature interneurons, and maturing intratelencephalic lineages. Genes associated with ASD converge on three functional programs--gene regulation, neuronal morphogenesis, and synaptic transmembrane signaling machinery--resolved from 28 ASD-associated networks, several of which are directly regulated by ASD genes including MEF2C, SOX11, and FOXP2. These programs are spatially patterned, with risk genes exhibiting an increasing anterior-to-posterior cortical expression gradient, anchored in the primary visual cortex and driven by excitatory neuron gene-regulatory programs. Finally, ASD risk genes associated with more severe developmental phenotypes show broader excitatory neuron enrichment and less interneuron involvement. Together, these findings anchor ASD genetic vulnerability to specific neurodevelopmental lineages, epochs, and molecular substrates, and delineate the features that distinguish ASD from comorbidities with broader developmental impacts.

genomics↗

bioRxiv2026

Mapping the genetic architecture of human cortical expansion and its links to neuropsychiatric disorders

Cortical expansion is a defining feature of human evolution and neurodevelopment, involving the tangential growth and gyrification of the cerebral cortex. Although disruptions to the expansion of the cortex are implicated in diverse brain-based disorders, the genetic architecture underlying this process remains undercharacterized. Here, we integrated GWAS data for five neuroanatomical phenotypes measured in up to 73,800 individuals to model a latent genomic factor capturing the shared genetic basis of cortical surface area, folding, curvature, gyrification, and intracranial volume. Using a multivariate framework, we mapped this pleiotropic architecture across biological scales, identifying novel effector genes, neural cell types, and developmental pathways involved in cortical expansion. Functional genomic evidence indicated that a diverse cellular ensemble contributes to the tangential growth and gyrification of the cortex during prenatal neurodevelopment, with progenitor cell lineages prominently involved. Regional analyses further revealed that genetic influences are spatially heterogeneous and organized along canonical anatomical, functional, and developmental gradients. Finally, cortical expansion exhibited substantial genetic overlap with neurodevelopmental, psychiatric, and neurological disorders, with shared genetic influences often concentrated in prefrontal cortical regions. Together, these findings map the genetic architecture of human cortical expansion and implicate it as a common etiological axis linking evolution, neurodevelopment, and health and disease.

genomics↗

bioRxiv2025

Morphogen-guided neocortical organoids recapitulate regional areal identity and model neurodevelopmental disorder pathology

The human neocortex exhibits characteristic regional patterning (arealization) critical for higher-order cognitive function. Disrupted arealization is strongly implicated in neurodevelopmental disorders (NDDs), but current neocortical organoid models largely fail to recapitulate this patterning, limiting mechanistic understanding. Here, we establish a straightforward method for generating arealized organoids through short-term early exposure to anterior (FGF8) or posterior (BMP4/CHIR-99021) morphogens. These treatments created distinct anterior and posterior signaling centers, supporting long-lasting polarization, which we validated with single-cell RNA sequencing that revealed area-specific molecular signatures matching prenatal human cortex. To demonstrate the utility of this platform, we modeled Fragile X Syndrome (FXS) in organoids with distinct anterior and posterior regional identities. FXS organoids showed highly disrupted SOX4/SOX11 expression gradients along the anterior-posterior axis, consistent with alterations found in autism spectrum disorder (ASD) and demonstrate how regional patterning defects may contribute to NDD pathology. Together, our study provides a robust platform for generating neocortical organoids with anterior-posterior molecular signatures and highlights the importance of modeling NDDs using experimental platforms with neuroanatomic specificity.

developmental biology↗

bioRxiv2025

A single cell multi-omic analysis identifies molecular and gene-regulatory mechanisms dysregulated in the developing Down syndrome neocortex

Down syndrome is the most common genetic cause of intellectual disability, presenting with cognitive, learning, memory, and language deficits. The cellular and molecular mechanisms driving this disorder remain unclear, limited by a lack of systematic studies in the developing human brain. Here, we leveraged single-nucleus multi-omics to profile the mid-gestation neocortex in a cohort of 26 donors. We observed a reduction in neural progenitors and corticothalamic neurons and concomitant increase of intratelencephalic neurons, accompanied by accelerated time to neuronal specification. We uncovered widespread changes in gene expression, chromatin accessibility and cell interaction networks impacting neurogenesis, specification and maturation and gene-regulatory networks directing these processes, including those downstream of transcription factors encoded in chromosome 21. Finally, we identified cell-specific molecular pathways shared with other neurodevelopmental disorders as well as heritability enrichment of GWAS signals in altered chromatin. Together, our data revealed a cascade of molecular dysregulation outlining the earliest steps in Down syndrome, providing a foundation for future therapeutic targets.

genomics↗

bioRxiv2025

Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of Fragile X mice and identifies EPAC2 as a therapeutic target.

Symptoms of Fragile X Syndrome (FXS), the leading monogenic cause of intellectual disability and autism, are thought to arise from an excitation/inhibition (E/I) imbalance. Here, we leverage cell type specific mRNA sequencing to profile molecular alterations of cortical excitatory and inhibitory neurons in Fmr1 knockout (KO) mice, integrating transcriptomic results with circuit and behavioral readouts to prioritize novel therapeutic targets. Differentially expressed genes (DEG) were largely upregulated in Camk2a expressing excitatory neurons but downregulated in Pvalb-expressing inhibitory neurons, and the underlying signaling pathways were often altered in opposite directions. Among the 184 DEGs that were concordantly dysregulated across both cell types, only Rapgef4 (Epac2) was also an FMRP target, an ASD risk gene and brain enriched. EPAC2 has been implicated in synaptic maturation and plasticity. Systemic administration of an EPAC2 antagonist restored cortical circuit function in Fmr1 KO mice and ameliorated sensory behavioral phenotypes. EPAC2 is a potential target for therapy in FXS.

neuroscience↗

bioRxiv2023

KAT6A mutations drive transcriptional dysregulation of cell cycle and Autism risk genes in an Arboleda-Tham Syndrome cerebral organoid model

Arboleda-Tham Syndrome (ARTHS, OMIM#616268) is a rare neurodevelopmental disorder caused by de novo mutations in KAT6A. Individuals with ARTHS typically exhibit varying degrees of intellectual disability, speech and language deficits and clinical manifestations across multiple systems that lead to abnormal: vision, craniofacial features, cardiac morphology, and gastrointestinal function. To gain insight into the potential neuropathological mechanisms underlying ARTHS, we investigate how KAT6A mutations disrupt in vitro brain development using induced pluripotent stem cells (iPSCs) and cerebral organoids (COs) derived from ARTHS patients harboring KAT6A nonsense mutations. In this study, we conducted comprehensive transcriptomic profiling by performing time-course experiments and generating short-read and long-read RNA sequencing (RNA-seq) data from undifferentiated iPSCs and COs at 15 and 25 days of neural differentiation. Our analysis revealed abnormal expression of 235 genes in ARTHS across all three timepoints examined. Notably, we observed persistent dysregulation of genes such as CTSF, ZNF229, PCDHB12, and PAK3. Additionally, we found a consistent enrichment of PTBP1-target genes among the upregulated genes in ARTHS at all three stages assessed by RNA-seq. During neural differentiation, we identified 980 genes that consistently display aberrant transcription in ARTHS at both CO stages. These genes are enriched for genes involved in cell fate determination through modulation of cell-cycle dynamics (e.g. E2F family) and cell-adhesion molecules (e.g. PCDH genes). Our findings indicate that ARTHS COs exhibit slower downregulation of pluripotency and cell cycle genes compared to controls and that this delay led to an overrepresentation of cycling human neural progenitor markers during neural differentiation in ARTHS. Finally, matching the variable neurodevelopment phenotypes in ARTHS, we discovered that the aberrantly expressed genes in ARTHS are enriched for genes associated with Autism Spectrum Disorder and Epilepsy, with a subset showing isoform-specific dysregulation. Strikingly, the same PTBP1-target genes were enriched amongst the genes that display differential isoform usage in ARTHS. For the first time, we demonstrate that KAT6A mutations lead to a delay in repressing pluripotency and cell cycle genes during neural differentiation, suggesting that prolonged activation of these gene networks disrupts the temporal dynamics of human brain development in ARTHS.

genetics↗

bioRxiv2022

The molecular genetic landscape of human brain size variation

Human brain size increases dynamically through early development, peaks in adolescence, and varies up to two-fold among adults. Although previous studies have elucidated changes in brain size across evolution, development, traits, and diseases, the molecular underpinnings of interindividual variation in brain size remain unknown. Here, we leverage postmortem brain RNA sequencing and estimates of brain weight (BW) in 2,531 individuals across three independent datasets, to identify 928 genes that show genome-wide significant associations with either higher or lower BW (BW+, BW-, respectively). These BW gene sets showed distinct neurodevelopmental trajectories and spatial patterns that mapped onto developmental, functional and cellular axes of brain organization. Expression differences among evolutionarily conserved BW genes were predictive of interspecies differences in brain size, and functional annotation of BW genes revealed enrichment for neurogenesis and cell-cell communication. Genome-wide, transcriptome-wide, and phenome-wide association analyses of in vivo neuroimaging phenotypes confirmed that the genetic regulation of BW-transcripts influences cortical surface area and volume, as well as behavioral traits related to brain function and disease. Cumulatively, our study represents a major step towards the goal of delineating the causal mechanisms of human brain size variation in health and disease.

neuroscience↗

bioRxiv2022

The genetics of cortical organisation and development: a study of 2,347 neuroimaging phenotypes

Our understanding of the genetic architecture of the human cerebral cortex is limited both in terms of the diversity of brain structural phenotypes and the anatomical granularity of their associations with genetic variants. Here, we conducted genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,843 individuals from the UK Biobank and the ABCD cohorts. These phenotypes include cortical thickness, surface area, grey matter volume, and measures of folding, neurite density, and water diffusion. We identified 4,349 experiment-wide significant loci associated with global and regional phenotypes. Multiple lines of analyses identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with surface area and volume specifically are associated with cephalic disorders. Finally, we identified complex inter-phenotype and inter-regional genetic relationships among the 13 phenotypes which reflect developmental differences among them. These analyses help refine the role of common genetic variants in human cortical development and organisation. One sentence summaryGWAS of 2,347 neuroimaging phenotypes shed light on the global and regional genetic organisation of the cortex, underlying cellular and developmental processes, and links to neurodevelopmental and cephalic disorders.

neuroscience↗

bioRxiv2022

GeneticsMakie.jl: A versatile and scalable toolkit for visualizing locus-level genetic and genomic data

With the continued deluge of results from genome-wide association and functional genomic studies, it has become increasingly imperative to quickly combine and visualize different layers of genetic and genomic data within a given locus to facilitate exploratory and integrative data analyses. While several tools have been developed to visualize locus-level genetic results, the limited speed, scalability, and flexibility of current approaches remains a significant bottleneck. Here, we present a Julia package GeneticsMakie.jl for high-performance genetics and genomics-related data visualization that enables fast, simultaneous plotting of hundreds of association results along with multiple relevant genomic annotations. Leveraging the powerful plotting and layout utilities from Makie.jl facilitates the customization and extensibility of every component of a plot, enabling generation of publication-ready figures. The GeneticsMakie.jl package is open source and distributed under the MIT license via GitHub (https://github.com/mmkim1210/GeneticsMakie.jl). The GitHub repository contains installation instructions as well as examples and documentation for built-in functions.

bioinformatics↗

bioRxiv2022

Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex

Autism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons of 59 postmortem human brains (27 ASD and 32 matched controls) in the superior temporal gyrus (STG) ranging from 2-73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in GABA (GAD1 and GAD2) and glutamate (SLC38A1) signaling pathways. In LCM neurons, AP-1 mediated neuroinflammation and insulin/IGF-1 signaling pathways were upregulated in ASD, while mitochondrial function, ribosome and spliceosome components were downregulated. GABA synthesizing enzymes GAD1 and GAD2 were both downregulated in ASD neurons. Alterations in small nucleolar RNAs (snoRNAs) associated with splicing events suggested interplay between snoRNA dysregulation and splicing disruption in neurons of individuals with ASD. Our findings supported the fundamental hypothesis of altered neuronal communication in ASD, demonstrated that inflammation was elevated at least in part in ASD neurons, and may reveal windows of opportunity for biotherapeutics to target the trajectory of gene expression and clinical manifestation of ASD throughout the human lifespan.

neuroscience↗

bioRxiv2021

Human Astrocytes Exhibit Tumor Microenvironment-, Age-, and Sex-Related Transcriptomic Signatures

Astrocytes are dynamic cells with important roles in brain function and neurological disease. There are notable species differences between human astrocytes and commonly used animal models. However, changes of the molecular attributes of human astrocytes across disease states, sex, and age are largely unknown, which is a barrier in understanding human astrocyte biology and its potential involvement in neurological diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. Here, we identified a robust transcriptomic signature of human astrocytes in the tumor-surrounding microenvironment, including upregulation of proliferation processes, along with downregulation of genes involved in ionic homeostasis and synaptic function, suggesting involvement of peri-tumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of astrocyte reactivity, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified some of the first transcriptomic evidence of sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurological disorders. Overall, genes involved in synaptic function exhibited dynamic changes in multiple conditions. This data provides powerful new insights into human astrocyte biology in several biologically relevant states, that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans. Significance StatementAstrocytes are an abundant class of cells playing integral roles in the central nervous system. Astrocyte dysfunction is implicated in a variety of human neurological diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found changes suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction, aging-associated decline in astrocyte-synapse interactions, ionic transport changes with brain maturation, and some of the first evidence of sexual dimorphism in human astrocytes. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.

neuroscience↗

bioRxiv2020

Broad transcriptomic dysregulation across the cerebral cortex in ASD

Classically, psychiatric disorders have been considered to lack defining pathology, but recent work has demonstrated consistent disruption at the molecular level, characterized by transcriptomic and epigenetic alterations.1-3 In ASD, upregulation of microglial, astrocyte, and immune signaling genes, downregulation of specific synaptic genes, and attenuation of regional gene expression differences are observed.1,2,4-6 However, whether these changes are limited to the cortical association areas profiled is unknown. Here, we perform RNA-sequencing (RNA-seq) on 725 brain samples spanning 11 distinct cortical areas in 112 ASD cases and neurotypical controls. We identify substantially more genes and isoforms that differentiate ASD from controls than previously observed. These alterations are pervasive and cortex-wide, but vary in magnitude across regions, roughly showing an anterior to posterior gradient, with the strongest signal in visual cortex, followed by parietal cortex and the temporal lobe. We find a notable enrichment of ASD genetic risk variants among cortex-wide downregulated synaptic plasticity genes and upregulated protein folding gene isoforms. Finally, using snRNA-seq, we determine that regional variation in the magnitude of transcriptomic dysregulation reflects changes in cellular proportion and cell-type-specific gene expression, particularly impacting L3/4 excitatory neurons. These results highlight widespread, genetically-driven neuronal dysfunction as a major component of ASD pathology in the cerebral cortex, extending beyond association cortices to involve primary sensory regions.

neuroscience↗

bioRxiv2020

Maternal immune activation during pregnancy alters early neurobehavioral development in nonhuman primate offspring

BackgroundHuman epidemiologic studies have implicated exposure to infectious or inflammatory insults during gestation in the etiology of neurodevelopmental disorders. Rodent models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant brain and behavior development in offspring. The nonhuman primate MIA model provides an opportunity to maximize the translational utility of this model in a species more closely related to humans. MethodsHere we evaluate the effects of MIA on brain and behavioral development in the rhesus monkey (Macaca mulatta). A modified form of the viral mimic, Polyinosinic-polycytidylic acid (PolyIC), was delivered to pregnant rhesus monkeys (n=14) in the late first trimester to stimulate a maternal immune response. Control dams received saline injections at the same gestational time points (n=10) or were untreated (n=4). ResultsMIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature and inflammatory cytokines. MIA-exposed offspring developed species typical milestones and demonstrate subtle changes in early in social development. However, magnetic resonance imaging demonstrated significant gray matter volume reductions in prefrontal and frontal cortices at 6, 12 and 24 months of age. ConclusionsThese findings provide new insights into the emergence of neuropathology in MIA-exposed primates and have implications for the pathophysiology of human psychiatric disorders associated with maternal gestational infection.

neuroscience↗

bioRxiv2020

Network signature of complement component 4 variation in the human brain identifies convergent molecular risk for schizophrenia

The most significant common variant association for schizophrenia (SCZ) reflects increased expression of the complement component 4A (C4A). Yet, it remains unclear how C4A interacts with other SCZ risk genes and whether the complement system is more broadly implicated in SCZ pathogenesis. Here, we integrate several existing, large-scale genetic and transcriptomic datasets to interrogate the functional role of the complement system and C4A in the human brain. Surprisingly, we find no significant genetic enrichment among known complement system genes for SCZ. Conversely, brain co-expression network analyses using C4A as a seed gene revealed that genes down-regulated when C4A expression increased exhibit strong and specific genetic enrichment for SCZ risk. This convergent genomic signal reflected neuronal, synaptic processes and was sexually dimorphic and most prominent in frontal cortical brain regions. Overall, these results indicate that synaptic pathways--rather than the complement system--are the driving force conferring SCZ risk.

genomics↗

bioRxiv2019

TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids

Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are emerging as an effective system to study the distinct features of the developing human brain and the underlying causes of many neurological disorders. While progress in organoid technology has been steadily advancing, many challenges remain including rampant batch-to-batch and cell line-to-cell line variability and irreproducibility. Here, we demonstrate that a major contributor to successful cortical organoid production is the manner in which hPSCs are maintained prior to differentiation. Optimal results were achieved using fibroblast-feeder-supported hPSCs compared to feeder-independent cells, related to differences in their transcriptomic states. Feeder-supported hPSCs display elevated activation of diverse TGF{beta} superfamily signaling pathways and increased expression of genes associated with naive pluripotency. We further identify combinations of TGF{beta}-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enable reproducible formation of brain structures suitable for disease modeling. HIGHLIGHTSO_LIhPSC maintenance conditions influence outcomes in cortical organoid formation C_LIO_LIIdentification of an intermediate pluripotency state optimal for cortical organoids C_LIO_LIFeeder support involves activation of diverse TGF{beta} signaling pathways C_LIO_LIThe organoid-promoting effects of feeders can be mimicked by a TGF{beta} factor mixture C_LI

developmental biology↗

bioRxiv2019

Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism

Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation from ASD and control brains to identify a convergent molecular subtype of ASD with shared dysregulation across both the epigenome and transcriptome. Focusing on this convergent subtype, we substantially expand the repertoire of differentially expressed genes in ASD and identify a component of upregulated immune processes that are associated with hypomethylation. We utilize eQTL and chromosome conformation datasets to link differentially acetylated regions with their cognate genes and identify an enrichment of ASD genetic risk variants in hyperacetylated noncoding regulatory regions linked to neuronal genes. These findings help elucidate how diverse genetic risk factors converge onto specific molecular processes in ASD.

genomics↗

bioRxiv2019

Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 CNV Mediated Risk for Neuropsychiatric Disorders

Background22q11.2 copy number variants (CNVs) are among the most highly penetrant genetic risk variants for developmental neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the specific mechanisms through which they confer risk remain unclear. MethodsUsing a functional genomics approach, we integrated transcriptomic data from the developing human brain, genome-wide association findings for SCZ and ASD, protein interaction data, and pathophysiological signatures of SCZ and ASD to: 1) organize genes into the developmental cellular and molecular systems within which they operate; 2) identify neurodevelopmental processes associated with polygenic risk for SCZ and ASD across the allelic frequency spectrum; and 3) elucidate pathways and individual genes through which 22q11.2 CNVs may confer risk for each disorder. ResultsPolygenic risk for SCZ and ASD converged on partially overlapping gene networks involved in synaptic function and transcriptional regulation, with ASD risk variants additionally enriched for networks involved in neuronal differentiation during fetal development. The 22q11.2 locus formed a large protein network that disproportionately affected SCZ- and ASD-associated neurodevelopmental networks, including loading highly onto synaptic and gene regulatory pathways. SEPT5, PI4KA, and SNAP29 genes are candidate drivers of 22q11.2 synaptic pathology relevant to SCZ and ASD, and DGCR8 and HIRA are candidate drivers of disease-relevant alterations in gene regulation. ConclusionsThe current approach provides a powerful framework to identify neurodevelopmental processes affected by diverse risk variants for SCZ and ASD, and elucidate the mechanisms through which highly penetrant multi-gene CNVs contribute to disease risk.

systems biology↗

bioRxiv2018

Genetic control of gene expression and splicing in the developing human brain

Most genetic risk for human diseases lies within non-coding regions of the genome, which is predicted to regulate gene expression, often in a tissue and stage specific manner. This has motivated building of extensive eQTL resources to understand how human allelic variation affects gene expression and splicing throughout the body, focusing primarily on adult tissue. Given the importance of regulatory pathways during brain development, we characterize the genetic control of the developing human cerebral cortical transcriptome, including expression and splicing, in 201 mid-gestational human brains, to understand how common allelic variation affects gene regulation during development. We leverage expression and splice quantitative trait loci to identify genes and isoforms relevant to neuropsychiatric disorders and brain volume. These findings demonstrate genetic mechanisms by which early developmental events have a striking and widespread influence on adult anatomical and behavioral phenotypes, as well as the evolution of the human cerebral cortex.\n\nHighlightsO_LIGenome wide map of human fetal brain eQTLs and sQTLs provides a new view of genetic control of expression and splicing.\nC_LIO_LIThere is substantial contrast between genetic control of transcript regulation in mature versus developing brain.\nC_LIO_LIWe identify novel regulatory regions specific to fetal brain development.\nC_LIO_LIIntegration of eQTLs and GWAS reveals specific relationships between expression and disease risk for neuropsychiatric diseases and relevant human brain phenotypes.\nC_LI

neuroscience↗