Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Science. 2024 May 24;384(6698):eadh0829. doi: 10.1126/science.adh0829. Epub 2024 May 24.
ABSTRACT
Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.
PMID:38781368 | DOI:10.1126/science.adh0829
![Google](https://www.google.com/images/branding/googlelogo/2x/googlelogo_light_color_92x30dp.png)
![Google Keep](https://www.gstatic.com/images/branding/product/1x/keep_48dp.png)
![Share on Linkedin](https://psychiatryai.com/wp-content/uploads/2023/10/linkedin-logo-png-2048-1.png)
Estimated reading time: 3 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Cool Evidence: Engaging Young People and Students in Real-World Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Real-Time Evidence Search [Psychiatry]
![](/wp-content/uploads/2024/04/pubmed.png)
AI Research
![](/wp-content/uploads/2024/05/Il5nR_nf_400x400-modified-1.png)
Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain Single-cell genomics and regulatory networks for 388 human brains Single-cell genomics and regulatory networks for 388 human brains Single-cell genomics and regulatory networks for 388 human brains Splicing-specific transcriptome-wide association uncovers genetic mechanisms for schizophrenia Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements Single-cell multi-cohort dissection of the schizophrenia transcriptome Single-cell multi-cohort dissection of the schizophrenia transcriptome A multi-layered integrative analysis reveals a cholesterol metabolic program in outer radial glia with implications for human brain evolution A multi-layered integrative analysis reveals a cholesterol metabolic program in outer radial glia with implications for human brain evolution Molecular cascades and cell type-specific signatures in ASD revealed by single-cell genomics Molecular cascades and cell type-specific signatures in ASD revealed by single-cell genomics Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets A transcriptomic atlas of the human brain reveals genetically determined aspects of neuropsychiatric health Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology Critical reasoning on the co-expression module QTL in the dorsolateral prefrontal cortex Integrated platform for multiscale molecular imaging and phenotyping of the human brain Integrated platform for multiscale molecular imaging and phenotyping of the human brain Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain Sex-Differential Gene Expression in Developing Human Cortex and Its Intersection With Autism Risk Pathways Quantitative Trait Locus Mapping in Placenta: A Comparative Study of Chorionic Villus and Birth Placenta Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 141 risk genes for Alzheimer's disease dementia Smoking-informed methylation and expression QTLs in human brain and colocalization with smoking-associated genetic loci Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders Establishing validated RT-qPCR workflow for the analysis of oligodendrocyte gene expression in the developing murine brain Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey Early Developmental Origins of Cortical Disorders Modeled in Human Neural Stem Cells Early Developmental Origins of Cortical Disorders Modeled in Human Neural Stem Cells Sex-biasing influence of autism-associated Ube3a gene overdosage at connectomic, behavioral, and transcriptomic levels Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program Whole-genome sequencing identifies novel genes for autism in Chinese trios An N-terminal and ankyrin repeat domain interactome of Shank3 identifies the protein complex with the splicing regulator Nono in mice Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq Evolutionary and biomedical implications of sex differences in the primate brain transcriptome Analysis of Evolutionary Conservation, Expression Level, and Genetic Association at a Genome-wide Scale Reveals Heterogeneity in Traits Across Polygenic Phenotypes Enhancer cooperativity can compensate for loss of activity over large genomic distances Identification of novel genetic loci and candidate genes for progressive ethanol consumption in diversity outbred mice Regulatory role of lncH19 in RAC1 alternative splicing: implication for RAC1B expression in colorectal cancer A de novo ARIH2 gene mutation was detected in a patient with autism spectrum disorders and intellectual disability RNA variant assessment using transactivation and transdifferentiation G272V and P301L mutations induce isoform specific tau mislocalization to dendritic spines and synaptic dysfunctions in cellular models of 3R and 4R tau frontotemporal dementia Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs The neocortical infrastructure for language involves region-specific patterns of laminar gene expression Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions A master regulator of opioid reward in the ventral prefrontal cortex A master regulator of opioid reward in the ventral prefrontal cortex A multi-ancestry cerebral cortex transcriptome-wide association study identifies genes associated with smoking behaviors Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data Brain region-specific alterations in gene expression trajectories in the offspring born from influenza a infected mice Comprehensive network modeling approaches unravel dynamic enhancer-promoter interactions across neural differentiation Genome-wide association study of delay discounting in Heterogeneous Stock rats Nuclear Genome-Encoded Mitochondrial OXPHOS Complex I Genes in Female Buffalo Show Tissue-Specific Differences Nuclear Genome-Encoded Mitochondrial OXPHOS Complex I Genes in Female Buffalo Show Tissue-Specific Differences CHG Lunchtime Lab Talks: Professor Christopher Buckley (Kennedy) Atypical dynamic neural configuration in autism spectrum disorder and its relationship to gene expression profiles Long-read RNA sequencing identifies region- and sex-specific C57BL/6J mouse brain mRNA isoform expression and usage
Evidence Blueprint
Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain Single-cell genomics and regulatory networks for 388 human brains Single-cell genomics and regulatory networks for 388 human brains Single-cell genomics and regulatory networks for 388 human brains Isoform-level transcriptome-wide association uncovers genetic risk mechanisms for neuropsychiatric disorders in the human brain Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences Splicing-specific transcriptome-wide association uncovers genetic mechanisms for schizophrenia Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements Deciphering the distinct transcriptomic and gene regulatory map in adult macaque basal ganglia cells Single-cell multi-cohort dissection of the schizophrenia transcriptome Single-cell multi-cohort dissection of the schizophrenia transcriptome Convergent and divergent genes expression profiles associated with brain-wide functional connectome dysfunction in deficit and non-deficit schizophrenia A multi-layered integrative analysis reveals a cholesterol metabolic program in outer radial glia with implications for human brain evolution A multi-layered integrative analysis reveals a cholesterol metabolic program in outer radial glia with implications for human brain evolution Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia Evaluating the regulatory function of non-coding autism-associated single nucleotide polymorphisms on gene expression in human brain tissue TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma Molecular cascades and cell type-specific signatures in ASD revealed by single-cell genomics Molecular cascades and cell type-specific signatures in ASD revealed by single-cell genomics Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets A transcriptomic atlas of the human brain reveals genetically determined aspects of neuropsychiatric health Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk Pleiotropy with sex-specific traits reveals genetic aspects of sex differences in Parkinson's disease Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology Critical reasoning on the co-expression module QTL in the dorsolateral prefrontal cortex Integrated platform for multiscale molecular imaging and phenotyping of the human brain Integrated platform for multiscale molecular imaging and phenotyping of the human brain Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain Sex-Differential Gene Expression in Developing Human Cortex and Its Intersection With Autism Risk Pathways Single-cell RNA-seq data analysis reveals functionally relevant biomarkers of early brain development and their regulatory footprints in human embryonic stem cells (hESCs) Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance Quantitative Trait Locus Mapping in Placenta: A Comparative Study of Chorionic Villus and Birth Placenta Exploring the interconnected between type 2 diabetes mellitus and nonalcoholic fatty liver disease: Genetic correlation and Mendelian randomization analysis Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 141 risk genes for Alzheimer's disease dementia Smoking-informed methylation and expression QTLs in human brain and colocalization with smoking-associated genetic loci Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders eQTL colocalization analysis highlights novel susceptibility genes in Autism Spectrum Disorders (ASD) Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species Establishing validated RT-qPCR workflow for the analysis of oligodendrocyte gene expression in the developing murine brain The Association of Hippocampal Long-Term Potentiation-Induced Gene Expression with Genetic Risk for Psychosis Sex-biased gene and microRNA expression in the developing mouse brain is associated with neurodevelopmental functions and neurological phenotypes Integrative analyses highlight functional regulatory variants associated with neuropsychiatric diseases Single-cell brain organoid screening identifies developmental defects in autism A Functional Schizophrenia-associated genetic variant near the TSNARE1 and ADGRB1 genes Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder Single-cell long-read sequencing in human cerebral organoids uncovers cell-type-specific and autism-associated exons Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey Epigenetic regulation of autophagy-related genes: Implications for neurodevelopmental disorders Early Developmental Origins of Cortical Disorders Modeled in Human Neural Stem Cells Early Developmental Origins of Cortical Disorders Modeled in Human Neural Stem Cells Sex-biasing influence of autism-associated Ube3a gene overdosage at connectomic, behavioral, and transcriptomic levels The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program Decoding m6A mRNA methylation by reader proteins in liver diseases