Won, H. et al. Front. https://doi.org/10.1038/s41588-022-01087-y, Combining SNP-to-gene linking strategies to identify disease genes and assess disease omnigenicity. Psychiatry 11, 71 (2021). Pedapati, E. V. et al. When SNPs are located near a gene, then it is postulated that the gene contributes to the variation under investigation. 52, 13551363 (2020). Wang, S.S.-H., Kloth, A. D. & Badura, A. Chang, X. 12, 24782492 (2017). Fifteen of these shared eQTLs control the same eGenes in fetal and adult cortex (e.g. Cells 8, 788 (2019). The significance of these associations in the developing cortex and how they contribute to the etiology of ASD remains to be empirically determined. However, studies have shown that Polycomb repressive complexes (PRC) can have a dual role in gene regulation during development45,46. PGBD1, ZKSCAN7, MPHOSPH9, TCF19 and VWA7); (b) decreases in transcript levels for VARS2; and (c) two genes (i.e. https://doi.org/10.1038/s41598-021-95447-z, DOI: https://doi.org/10.1038/s41598-021-95447-z. de la Torre-Ubieta, L., Won, H., Stein, J. L. & Geschwind, D. H. Advancing the understanding of autism disease mechanisms through genetics. 344 ASD-associated SNPs (p<5108) represented in both fetal and adult cortex-specific eQTL datasets were run through the CoDeS3D pipeline to identify 81 and 44 spatially regulated genes in fetal and adult cortical tissues, correspondingly. ASD-associated SNPs (p<5108, n=454) were downloaded from the GWAS Catalog (Supplementary Tables 1 and 2). https://doi.org/10.1038/s41588-022-01093-0. CAS ASD-associated eQTLs regulate 81 genes in fetal and 44 genes in adult cortical tissues (Fig. 69, 101468 (2020). Nat. Previous research has reported shared neurobiological and cellular processes associated with differences in cortical thickness across six psychiatric disorders (i.e. 11, 27 (2017). By contrast, 9 fetal cortex-specific genes (i.e. These eQTLs were also linked to other psychiatric disorders (e.g. Estes, M. L. & McAllister, A. K. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Analyzing the Effects of Genetic Variation in Noncoding - ScienceDirect This will revolutionize the medical field in the future. Repeating similar analysis in other brain (e.g. expression quantitative trait loci or eQTLs) in the fetal and adult cortex, respectively. STRING v11: Proteinprotein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. We obtained ASD-associated SNPs from nine GWAS studies that were performed in cohorts containing individuals of mostly European ancestry (Supplementary Table 2). dorsolateral prefrontal cortex cells)12 Hi-C chromatin interaction libraries (Supplementary Table 1). *Gene transcript levels are associated with the same eQTL in both the fetal and adult cortical tissues. The resulting expression (GTEx_Analysis_v8_eQTL_expression_matrices.tar) and covariates (GTEx_Analysis_v8_eQTL_covariates.tar.gz) data were downloaded from GTEx website (https://www.gtexportal.org/home/datasets, 01/05/2020). 78, 4763 (2021). Roles for these component gene expression processes in ASD are supported by existing studies (e.g. Google Scholar. volume11, Articlenumber:15867 (2021) 9, 5198 (2018). The proteinprotein interaction (PPIs) network serves as a foundation for cellular signalling circuitry, which mediates cellular responses to environmental and genetic cues. The regulatory effects can occur in trans (e.g. In order to study spatial regulatory interactions in fetal and adult cortical tissues, we analysed two fetal brain-specific (i.e. Roadmap Epigenomics Consortium et al. For example, if the user wants to find SNPs that might affect gene expression, he/she may choose to sort SNPs by regulatory potential score before sorting SNPs by function score. Sunwoo, M. et al. Genom. 2, Supplementary Table 5). & Wang, K. wANNOVAR: Annotating genetic variants for personal genomes via the web. As such, restriction fragments were used to identify regulatory interactions between SNPs and genes (Fig. By contrast, in the adult cortex they largely affect immune pathways. Moreover, Trlungeanu et al. Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR): Study protocol for a randomised controlled trial. Psychiatry 9, 298 (2019). 12, 230 (2018). Neurosci. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). All RNA-seq data were processed according to the GTEx pipeline (https://github.com/broadinstitute/gtex-pipeline/tree/master/rnaseq) (Supplementary Fig. Removal of HLA genes from analyses of the adult cortex gene set identified a retained enrichment for immune-related processes (e.g. When present within a coding sequence and leading to an amino acid change (referred to as a non-synonymous SNP or mutation), they can modify the protein's activity. Finally, significant cortex-specific eQTL-eGene interactions were identified using the Benjamini-Hochberg (BH) FDR correction to adjust the eQTL p values (FDR<0.05) (Supplementary Table 3). Firstly, SNPs can mark regulatory regions that affect distant genes (i.e. Genet. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. However, this would require randomised control trials in animals prior to testing in humans. Studies have previously reported associations between ASD and: (1) schizophrenia36; (2) depression37; (3) ADHD38,39; (4) bipolar disorder40; and other co- and multimorbidities24,41,42. SF3B1 and THOC7 were also associated with ASD-eQTLs within the adult cortex. And by View the full answer However, more than 84% of the identified spatially regulated genes were novel and have not previously been linked to autism or curated in AutDB. The mutational constraint spectrum quantified from variation in 141,456 humans. GWAS has been commonly used in identifying SNPs associated with diseases or clinical phenotypes or traits. BCFtools were used to set variant IDs according to the GTEx variant ID format (e.g. Genome-wide association study of traits in sacred lotus uncovers MITE-associated variants underlying stamen petaloid and petal number variations. Article SNPs) among conditions was counted for each bootstrap iteration. There is no fundamental reason why the same regulatory elements must or must not impact on the same gene in different tissues, or at different stages of development. Identification of functional single nucleotide polymorphisms in the branchpoint site. 2, Supplementary Table 5). For gene analysis, we resampled eGenes from the list of all genes in the genome (GENCODE transcript model version 26). The mapping is shown for A the 1D linear genome and B the 3D genome structure constructed at the Hi-C resolution of 10 kbp. RNA-seq data were processed by GTEx using RNA-seq analysis (https://github.com/broadinstitute/gtex-pipeline/tree/master/rnaseq) and eQTL discovery (https://github.com/broadinstitute/gtex-pipeline/tree/master/qtl) pipelines to calculate normalized gene expression and covariates. High-throughput identification of human SNPs affecting regulatory element activity. Finucane, H. K. et al. All datasets and software used in the analysis are listed in Supplementary Table 1. Secondly, in our manuscript we focused on cortex-specific eQTL-gene connections. Frontiers | From GWAS to Function: Using Functional Genomics to 4, Supplementary Table 9). eQTL datasets for fetal and adult cortex were obtained from Walker et al.20 and GTEx v821, correspondingly. The dynamic 3D genome in gametogenesis and early embryonic development. We also identified two genes that had multiple eQTLs where substitution of the SNP with the minor allele had opposing associations with the genes transcript levels (Fig. An alternative explanation is that the existence of the shared eQTLs between the multimorbid conditions is due to ambiguity in the phenotyping that was used in the GWAS studies that characterised the phenotype associated-SNPs. 53, 15271533 (2021). Therefore, characterizing the functional impacts (i.e. This observation is consistent with: (1) a comorbid association between ASD and schizophrenia25; or (2) a lack of resolution and precision in defining the ASD and schizophrenia phenotypes, and thus possible false positives in GWASs26. Nucleic Acids Res. Dysregulation of fatty acid metabolism in early brain development may be a risk factor or marker for early-onset of ASD48. Backman, J. D. et al. Boyle, E. A., Li, Y. I. Our findings highlight potential mechanisms through which ASD-associated variants potentially contribute to ASD development (fetal) and onset/maintenance (adult). View Solution Related Answers how could SNP's contribute to gene regulation?. Thirdly, the brain regions that are involved in the etiology of ASD remain difficult to determine. PRC2-associated chromatin contacts in the developing limb reveal a possible mechanism for the atypical role of PRC2 in HoxA gene expression. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Each SNP represents a difference in a single DNA building block, called a "nucleotide." For example, an SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA. Unable to load your collection due to an error, Unable to load your delegates due to an error. & Zhang, Z. ASD is widely considered to be a neurodevelopmental disorder resulting from functional changes within the brain. PubMed This data-driven approach enables the discovery of SNPs whose alleles impact gene regulation by miRNAs, with functional consequences for tumor biology. Nat. ZSCAN23 and LY6G5C) whose transcript levels increase or decrease, dependent upon specific eQTL. The GTEx eQTL discovery (https://github.com/broadinstitute/gtex-pipeline/tree/master/qtl) pipeline was further used to calculate normalized gene expression and covariates. The author declares no competing interests. Nat. Single nucleotide polymorphism (SNP) is the simplest form of DNA variation among individuals. An AUTS2-Polycomb complex activates gene expression in the CNS. This network illustrates potential evidence for gene regulation related to RA-associated SNPs, and may provide comprehensive information for subsequent functional analyses and experiments. PHACTR3, BAG6, CSNK2B, SF3B1, PPP1R16B, FADS2, RTN1, TBL1X and ENAH) and 5 adult cortex-specific genes (i.e. Benefits and limitations of genome-wide association studies. Genet. However, the remaining 15 eQTLs are associated with different eGenes in adult and fetal cortical tissues (Supplementary Table 4). To evaluate possible commonalities among ASD and other phenotypes at the eQTL level in the fetal and adult cortex, we intersected the identified ASD-associated eQTLs with SNPs associated with other traits in the GWAS catalog (p<5108, assessed on 26/08/2020). Systematic localization of common disease-associate variation in regulatorty DNA. Rev. Trials 18, 131 (2017). Overview of the analysis pipeline used in this study. Bootstrapping analysis revealed that these overlaps are significant (p<0.01, n=10,000). Collectively, these observations are consistent with changes in the regulation of subsets of stable and remodelled spatial eQTLs, over the course of brain development, being associated with a predisposition to ASD. How could SNPs contribute to gene regulation? Article In this study, we integrated four distinct levels of biological information (GWAS, eQTL, genome organization [Hi-C] and proteinprotein interactions [PPI] networks) to translate genetic variation associated with ASD to the biological pathways that are affectedthrough alterations to the transcription levels of their component proteins in fetal and adult cortical tissues. HLA-DRB1, HLA-DMB and HLA-DMA; associated with exogenous peptide processing) genes. Husson, T. et al. government site. Imputation accuracy was assessed by filtering variants by info score (INFO<0.8). 48, 552555 (2016). When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene's function. Roles for immune dysfunction in ASD etiology are increasingly being identified57,58,59. Genetic control of expression and splicing in developing human brain informs disease mechanisms. Simply assigning function to the adjacent gene increases the number of false positive gene associations73. The expression level in an indivisual is measured by the measuring the Trascribed mRNA, by the method of Northern blot . J Recept Signal Transduct Res. Within-family IDs were used as sample IDs in the output vcf file (recode vcf-iid bgz). Firstly, there was a significant enrichment of ASD-eQTLs within loci that are annotated as being regulated by PolyComb within the fetal, but not adult, cortex. PubMed Central Understanding the mechanisms underlying the effects of SNPs that . SNPs are located in gene promoters, exons, introns as well as 5'- and 3'- untranslated regions (UTRs) and affect gene expression by different mechanisms. Genet. Genetic variants were filtered based on HardyWeinberg equilibrium p<1106, minor allele frequency 0.01 and variant missing genotype rate 0.05. Louvain clustering analysis identified seven highly connected PPI modules within fetal cortex. How far from the SNP may the causative genes be?. eCollection 2022. 45, 984994 (2013). Wang J, Su W, Zhang T, Zhang S, Lei H, Ma F, Shi M, Shi W, Xie X, Di C. Cell Death Dis. PubMed Finally, we evaluated identified eQTL SNP associations with other phenotypes in the GWAS Catalog (downloaded on 26/08/2020) (Supplementary Table 4). 44, 60466054 (2016). PubMedGoogle Scholar. For example, rs4481150 eQTL is present in both fetal and adult eQTL databases. Similar approaches, in combination with existing and future clinical studies of ASD will contribute to individualized mechanistic understanding of ASD etiology in early brain development and adulthood. PDF GENETIC ASSOCIATION STUDIES OF COMPLEX DISEASES ByYen - arXiv Genotypes (derived by Array Genotyping) for 219 fetal brain donors20 were downloaded from dbGaP (05/06/2020), processed and prepared in the GTEx format (Supplementary Fig. This approach, in combination with clinical studies on ASD, will contribute to individualized mechanistic understanding of ASD development. Science 353, 772777 (2016). Most of these fetal ASD-associated eQTLs located within the Polycomb-repressed eQTLs were not identified as eQTLs in the adult cortex (Fig. 3, 1 (2011). Science 362,eaat8127 (2018). 1, Supplementary Table 3). Google Scholar. Single-Nucleotide Polymorphism - an overview | ScienceDirect Topics The same reference genome and annotation files were used to calculate expression for fetal brain RNA-seq data. Westra, H.-J. Normalized vcf files were further validated using VCFtools (v0.1.15). Nat. Dev. cortical plate and germinal zone neurons), or adult (i.e. 51, 431444 (2019). Over 11 million proteinprotein interactions (PPIs) were downloaded from STRING database (version 11.0) and combined with cortex-specific expression data (GTEx v8 or Walker et al. regQTLs: Single nucleotide polymorphisms that modulate microRNA - PLOS 45, 12381243 (2013). 1). Removal of all HLA genes from the analysis, identified enrichments for genes involved in fatty acid metabolism and processes related to the endoplasmic-reticulum-associated protein degradation (ERAD) pathway within fetal cortex. Proteins that were not annotated in the expression datasets were also removed from the CSPPI network. Cardiovasc. [34] Genome-wide genetic data can be generated by multiple technologies, including SNP array and whole genome sequencing. Overall, our findings highlight potential regulatory mechanisms and pathways important for the etiology of ASD in early brain development and adulthood. Top five genotype principal components (calculated using compute_genotype_pcs.py script from https://github.com/broadinstitute/gtex-pipeline/tree/master/genotype), 30 PEER factors, sex and genotyping platform were used as covariates in the eQTL analysis. 2022 Sep 23;13:973347. doi: 10.3389/fpls.2022.973347. PPI network analyses have been used to discover essential proteins, clusters of proteins with similar, overlapping or combinatorial functions, and associated pathways involved in tissue-specific contributions to ASD etiology17,18. 370, 12091219 (2014). The identified ASD-associated eQTLs were annotated using wANNOVAR tool77 (http://wannovar.wglab.org/, 10/08/2020) to obtain information about the locus they tagged (Supplementary Table 4). 2023 Apr;11(2):e003164. Accessibility Quality control metrics and gene-level expression data were calculated using RNA-seQC (v2.3.6) on the basis of GENCODE v26 gene annotation (gencode.v26.GRCh38.genes.gtf, gs://gtex-resources). Raudvere, U. et al. 57, 580594 (2015). HLA-DMA and BAG6 gene transcript levels are associated with distinct sets of eQTLs in both fetal and adult cortical tissues (Supplementary Fig. The GWAS Catalog is a publicly available database of all published GWAS studies76. 45, D139D144 (2017). Question: how could SNP's contribute to gene regulation? - Chegg the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in What are single nucleotide polymorphisms (SNPs)? - MedlinePlus Physiol. *Hi-C datasets for cortical plate and germinal zone neurons (phs001190.v1.p1) were obtained from Won et al.19, Hi-C datasets for adult dorsolateral prefrontal cortex cells were obtained from Schmitt et al.12. 1). BTN2A2 and BTN3A1 in the adult and fetal cortex, respectively). 47, 165175 (2019). Genomic and metabolic profiling of two tomato contrasting cultivars for tolerance to Tuta absoluta. Furthermore, we constructed fetal and adult cortex-specific proteinprotein interaction networks and identified that ASD-associated regulatory SNPs impact on immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome in the fetal cortex. The resulting vcf file was converted to plink format and information on sample sex included. Google Scholar. associated with an increase or reduction in transcript levels; Supplementary Fig. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Different eQTLs are often associated with the gene transcript levels, although the effects of the minor allele are typically similar for the gene in question (i.e. Each bootstrap iteration generated samples of the same size as in the tested sample for tested condition. (c) All ASD-associated eQTLs in adult cortex (n=58) and approximately 78 (97.5%) of the ASD-associated eQTLs within the fetal cortex are located within non-coding genomic regions (Supplementary Table 5). Finally a number of fetal (n=50) and adult (n=28) cortex-specific eQTLs were observed (Supplementary Table 3). Google Scholar. Polycomb proteins are known to be involved in transcriptional silencing43,44. Cis-eQTL SNPs are the SNPs that are within or around the corresponding gene, and trans-eQTL SNPs are those that are far away or even on dierent chromosomes. In this manuscript we integrated data on cortex-specific spatial chromatin interactions (i.e. By contrast, the rs1518367 eQTL is associated with reduced transcript levels for SF3B1 only in fetal cortex. Nature 516, 349354 (2014). The PPI clusters with unknown functions (Fig. Nat. Nancy Y. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Phenotypes were defined as the mapped traits associated with the SNP in the GWAS Catalog. JOS was also funded by a Royal Society of New Zealand Marsden Fund [Grant 16-UOO-072]. BCFtools (v1.10.2) was used to exclude genetic variants on chromosome 0 (omitted due to mapping to multiple locations) and chromosome 25 (XY pseudoautosomal region), to rename chromosomes 23 (X), 24 (Y) and 26 (MT), to fix REF allele, to check samples sex and to normalize the output vcf file to the GRCh37 reference genome (human_g1k_v37.fasta.gz, downloaded from ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/technical/reference/, 01/07/2020). These simple changes can be of transition or transversion type and they occur throughout the genome at a frequency of about one in 1,000 bp. In total, 663,956 variants passed QC filters. This is further complicated by tissue averaging across the complex cellular organization and composition which is also different in early development and adulthood. PubMed Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. A large number of genes associated with various cancer types contain single nucleotide polymorphisms (SNPs). 3). By contrast, the adult PPI gene set contained three highly connected modules, two of which were not associated with specific pathway, and one of which was enriched for immune pathways. ASD-associated eQTLs mark loci that spatially regulate the expression of genes involved in the fetal brain, in the adult brain, or both. and JavaScript. Mech. Book In conclusion, we have identified clinically relevant putative functional impacts for ASD-associated genetic variants within fetal and adult cortical tissues. Since the output is an easily manipulated spreadsheet, the user can sort the SNPs to highlight different SNP features. As we observed for other pathways, there was a developmental separation in the immune pathways that were affected in the fetal and adult cortical tissues. Hughes, H. K., Mills Ko, E., Rose, D. & Ashwood, P. immune dysfunction and autoimmunity as pathological mechanisms in autism spectrum disorders. Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments. Briefly, merged fastq files were aligned to the GRCh38 reference genome (Homo_sapiens_assembly38_noALT_noHLA_noDecoy.fasta, gs://gtex-resources) using STAR (v2.5.3a). The size of each node depends on the protein expression levels (no missing values and minimum expression level >0 TPM) in the corresponding cortical tissue. Commun. Fetal and adult cortical tissue-specific PPI networks with immune and growth related phenotypes are affected by ASD-associated eQTLs. Transl. Synaptic Neurosci. From these CSPPI networks we identified 42 ASD-associated PPIs within the fetal gene set, and 10 ASD-associated PPIs from the adult cortical tissue gene set (Fig. Hum. Google Scholar. Szklarczyk, D. et al. SNPselector: a web tool for selecting SNPs for genetic association You are using a browser version with limited support for CSS. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Smith, R. M. & Sadee, W. Synaptic signaling and aberrant RNA splicing in autism spectrum disorders. When SNPs occur within a gene or in a regulatory region near a gene, they often play a more direct role in the disease by affecting the function of the gene, either causing it to make a protein that works too well, or has less activity than normal, or completely stops its production. Lai, M.-C., Lombardo, M. V. & Baron-Cohen, S. Autism. 47, W191W198 (2019). Huang C, Guo Y, Li W, Xiang B, Zeng J, Zhou F, She L, Zhang P, Wang S, Liu B, Dai Q, Yang M. BMJ Open Diabetes Res Care. Transl. Ann. Boulanger-Bertolus, J., Pancaro, C. & Mashour, G. A. These differences can underlie susceptibility to common diseases, human traits, and differential responses to drugs. We contend that changing the transcription levels of these genes, alters biological pathways that modify an individuals predisposition to develop ASD. 2009;29(5):286-91. doi: 10.1080/10799890902911948. However, the potential contributions of cortex-specific developmental changes to these networks in ASD development have yet to be investigated. The number of shared items (e.g. An official website of the United States government. Prevalence and outcomes of young people with concurrent autism spectrum disorder and first episode of psychosis. & Jernigan, T. L. The basics of brain development. Aranda, S., Mas, G. & Di Croce, L. Regulation of gene transcription by Polycomb proteins. aberrant splicing and ASD52,53; upregulation of ribosomal protein genes and a higher ribosomal gene dosage can be linked to ASD risk and severity54,55). All genomic positions and SNP annotations were obtained for human genome reference build hg38 (GRCh38) release 75. Paternally inherited cis-regulatory structural variants are associated with autism. Google Scholar. Notably, we found that ASD-eQTL associated changes in transcript levels occurred in adult cortex immune pathways that were associated with processing of exogenous antigen. This improved knowledge may provide a starting point for the development of new, useful SNP markers for medical testing and a safer individualized medication to treat the most common devastating disorders. Mol. Mechanism of HPSE Gene SNPs Function: From Normal Processes - Springer This site needs JavaScript to work properly. J. Mol. Imputed genotypes were filtered for HardyWeinberg equilibrium p<1106, variant missing genotype rate 0.05 and minor allele frequency 0.01. The significance level was determined using the BH algorithm (FDR<0.05). SNPs can also be used to track the inheritance of disease genes within families. We have shown that the transcript levels of genes, whose encoded proteins are known to contribute to immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome are affected in the fetal cortex. Duplicated mapped reads were marked using Picard MarkDuplicates module (v2.21.4). Neurosci. 2008 Sep 11;128(17):1951-5. Get what matters in translational research, free to your inbox weekly. To obtain Nucleic Acids Res. Nucleic Acids Res. Genet. Hudson, C. C., Hall, L. & Harkness, K. L. Prevalence of depressive disorders in individuals with autism spectrum disorder: A meta-analysis. Fetal and adult ASD-associated eQTLs were also associated with schizophrenia, unipolar depression, ADHD, bipolar disorder, anorexia nervosa and obsessivecompulsive disorder (Supplementary Fig. Therefore, identification of numerous variations in genes and analysis of their effects may lead to a better understanding of their impact on gene function and health of an individual. Genes depleted for null variants were defined as having pLI>0.9. Genome Res. Fadason, T., Schierding, W., Lumley, T. & OSullivan, J. M. Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities. Cell. Here, we integrated four distinct levels of biological information (GWAS, eQTL, spatial genome organization and proteinprotein interactions) to identify potential regulatory impacts of ASD-associated SNPs (p<5108) on biological pathways within fetal and adult cortical tissues. Fetal ASD-associated eQTLs were located within quiescent/low transcribed (n=31), weak transcription (n=18), week repressed Polycomb (n=14) and repressed Polycomb (n=10) regions (Fig. 2b). van Arensbergen, J. et al. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Secondly, the finding that these ASD-eQTLs are associated with both increases and decreases in transcript levels is consistent with the up- and downregulation of the target genes.
