'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Sun, 20 Jan 2019 23:48:41 EST Sun, 20 Jan 2019 23:48:41 EST jirtle@radonc.duke.edu james001@jirtle.com Host and microbiome multi-omics integration: applications and methodologies. Wang Q, Wang K, Wu W, Giannoulatou E, Ho JWK, Li L
Biophys Rev (Jan 2019)

The study of the microbial community-the microbiome-associated with a human host is a maturing research field. It is increasingly clear that the composition of the human's microbiome is associated with various diseases such as gastrointestinal diseases, liver diseases and metabolic diseases. Using high-throughput technologies such as next-generation sequencing and mass spectrometry-based metabolomics, we are able to comprehensively sequence the microbiome-the metagenome-and associate these data with the genomic, epigenomics, transcriptomic and metabolic profile of the host. Our review summarises the application of integrating host omics with microbiome as well as the analytical methods and related tools applied in these studies. In addition, potential future directions are discussed.]]>
Wed, 31 Dec 1969 19:00:00 EST
Transcriptional regulation of normal human mammary cell heterogeneity and its perturbation in breast cancer. Pellacani D, Tan S, Lefort S, Eaves CJ
EMBO J (Jan 2019)

The mammary gland in adult women consists of biologically distinct cell types that differ in their surface phenotypes. Isolation and molecular characterization of these subpopulations of mammary cells have provided extensive insights into their different transcriptional programs and regulation. This information is now serving as a baseline for interpreting the heterogeneous features of human breast cancers. Examination of breast cancer mutational profiles further indicates that most have undergone a complex evolutionary process even before being detected. The consequent intra-tumoral as well as inter-tumoral heterogeneity of these cancers thus poses major challenges to deriving information from early and hence likely pervasive changes in potential therapeutic interest. Recently described reproducible and efficient methods for generating human breast cancers in immunodeficient mice transplanted with genetically altered cells now offer a promising alternative to investigate initial stages of human breast cancer development. In this review, we summarize current knowledge about key transcriptional regulatory processes operative in these partially characterized subpopulations of normal human mammary cells and effects of disrupting these processes in experimentally produced human breast cancers.]]>
Wed, 31 Dec 1969 19:00:00 EST
Multi-omics analyses reveal epigenomics basis for cotton somatic embryogenesis through successive regeneration acclimation process. Li J, Wang M, Li Y, Zhang Q, Lindsey K, Daniell H, Jin S, Zhang X
Plant Biotechnol J (Feb 2019)

Plant regeneration via somatic embryogenesis is time-consuming and highly genotype-dependent. The plant somatic embryogenesis process provokes many epigenetics changes including DNA methylation and histone modification. Recently, an elite cotton Jin668, with an extremely high regeneration ability, was developed from its maternal inbred Y668 cultivar using a Successive Regeneration Acclimation (SRA) strategy. To reveal the underlying mechanism of SRA, we carried out a genome-wide single-base resolution methylation analysis for nonembryogenic calluses (NECs), ECs, somatic embryos (SEs) during the somatic embryogenesis procedure and the leaves of regenerated offspring plants. Jin668 (R4) regenerated plants were CHH hypomethylated compared with the R0 regenerated plants of SRA process. The increase in CHH methylation from NEC to EC was demonstrated to be associated with the RNA-dependent DNA methylation (RdDM) and the H3K9me2-dependent pathway. Intriguingly, the hypomethylated CHH differentially methylated regions (DMRs) of promoter activated some hormone-related and WUSCHEL-related homeobox genes during the somatic embryogenesis process. Inhibiting DNA methylation using zebularine treatment in NEC increased the number of embryos. Our multi-omics data provide new insights into the dynamics of DNA methylation during the plant tissue culture and regenerated offspring plants. This study also reveals that induced hypomethylation (SRA) may facilitate the higher plant regeneration ability and optimize maternal genetic cultivar.]]>
Wed, 31 Dec 1969 19:00:00 EST
Considerations when processing and interpreting genomics data of the placenta. Konwar C, Del Gobbo G, Yuan V, Robinson WP
Placenta (Jan 2019)

The application of genomic approaches to placental research has opened exciting new avenues to help us understand basic biological properties of the placenta, improve prenatal screening/diagnosis, and measure effects of in utero exposures on child health outcomes. In the last decade, such large-scale genomic data (including epigenomics and transcriptomics) have become more easily accessible to researchers from many disciplines due to the increasing ease of obtaining such data and the rapidly evolving computational tools available for analysis. While the potential of large-scale studies has been widely promoted, less attention has been given to some of the challenges associated with processing and interpreting such data. We hereby share some of our experiences in assessing data quality, reproducibility, and interpretation in the context of genome-wide studies of the placenta, with the aim to improve future studies. There is rarely a single "best" approach, as that can depend on the study question and sample cohort. However, being consistent, thoroughly assessing potential confounders in the data, and communicating key variables in the methods section of the manuscript are critically important to help researchers to collaborate and build on each other's work.]]>
Wed, 31 Dec 1969 19:00:00 EST
Integrating regulatory features data for prediction of functional disease-associated SNPs. Dong SS, Guo Y, Yao S, Chen YX, He MN, Zhang YJ, Chen XF, Chen JB, Yang TL
Brief Bioinform (Jan 2019)

Genome-wide association studies (GWASs) are an effective strategy to identify susceptibility loci for human complex diseases. However, missing heritability is still a big problem. Most GWASs single-nucleotide polymorphisms (SNPs) are located in noncoding regions, which has been considered to be the unexplored territory of the genome. Recently, data from the Encyclopedia of DNA Elements (ENCODE) and Roadmap Epigenomics projects have shown that many GWASs SNPs in the noncoding regions fall within regulatory elements. In this study, we developed a pipeline named functional disease-associated SNPs prediction (FDSP), to identify novel susceptibility loci for complex diseases based on the interpretation of the functional features for known disease-associated variants with machine learning. We applied our pipeline to predict novel susceptibility SNPs for type 2 diabetes (T2D) and hypertension. The predicted SNPs could explain heritability beyond that explained by GWAS-associated SNPs. Functional annotation by expression quantitative trait loci analyses showed that the target genes of the predicted SNPs were significantly enriched in T2D or hypertension-related pathways in multiple tissues. Our results suggest that combining GWASs and regulatory features data could identify additional functional susceptibility SNPs for complex diseases. We hope FDSP could help to identify novel susceptibility loci for complex diseases and solve the missing heritability problem.]]>
Wed, 31 Dec 1969 19:00:00 EST
Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks. Rubin AJ, Parker KR, Satpathy AT, Qi Y, Wu B, Ong AJ, Mumbach MR, Ji AL, Kim DS, Cho SW, Zarnegar BJ, Greenleaf WJ, Chang HY, Khavari PA
Cell (Jan 2019)

Here, we present Perturb-ATAC, a method that combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by assay of transposase-accessible chromatin with sequencing (ATAC-seq). We applied Perturb-ATAC to transcription factors (TFs), chromatin-modifying factors, and noncoding RNAs (ncRNAs) in ∼4,300 single cells, encompassing more than 63 genotype-phenotype relationships. Perturb-ATAC in human B lymphocytes uncovered regulators of chromatin accessibility, TF occupancy, and nucleosome positioning and identified a hierarchy of TFs that govern B cell state, variation, and disease-associated cis-regulatory elements. Perturb-ATAC in primary human epidermal cells revealed three sequential modules of cis-elements that specify keratinocyte fate. Combinatorial deletion of all pairs of these TFs uncovered their epistatic relationships and highlighted genomic co-localization as a basis for synergistic interactions. Thus, Perturb-ATAC is a powerful strategy to dissect gene regulatory networks in development and disease.]]>
Wed, 31 Dec 1969 19:00:00 EST
Smooth Muscle Contact Drives Endothelial Regeneration by BMPR2-Notch1-Mediated Metabolic and Epigenetic Changes. Miyagawa K, Shi M, Chen PI, Hennigs JK, Zhao Z, Wang M, Li CG, Saito T, Taylor S, Sa S, Cao A, Wang L, Snyder MP, Rabinovitch M
Circ Res (Jan 2019)

Maintaining endothelial cells (EC) as a monolayer in the vessel wall depends on their metabolic state and gene expression profile, features influenced by contact with neighboring cells such as pericytes and smooth muscle cells (SMC). Failure to regenerate a normal EC monolayer in response to injury can result in occlusive neointima formation in diseases such as atherosclerosis and pulmonary arterial hypertension.]]>
Wed, 31 Dec 1969 19:00:00 EST
Simultaneous Targeted Methylation Sequencing (sTM-Seq). Asmus N, Papale LA, Madrid A, Alisch RS
Curr Protoc Hum Genet (Jan 2019)

Mapping patterns of DNA methylation throughout the epigenome are critical to our understanding of several important biological and regulatory functions, such as transcriptional regulation, genomic imprinting, and embryonic development. The development and rapid advancement of next-generation sequencing (NGS) technologies have provided clinicians and researchers with accurate and reliable read-outs of genomic and epigenomic information at the nucleotide level. Such improvements have significantly lowered the cost required for genome-wide sequencing, facilitating the vast acquisition of data that has led to many improvements in patient care. However, the torrid rate of NGS data generation has left targeted validation approaches behind, including the confirmation of epigenetic marks such as DNA methylation. To overcome these shortcomings, we present a rapid and robust protocol for the parallel examination of multiple methylated sequences that we have termed simultaneous targeted methylation sequencing (sTM-Seq). Key features of this technique include the elimination of the need for large amounts of high-molecular weight DNA and the nucleotide specific distinction of both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Moreover, sTM-Seq is scalable and can be used to investigate multiple loci in dozens of samples within a single sequencing run. By utilizing freely available web-based software and universal primers for multipurpose barcoding, library preparation, and customized sequencing, sTM-Seq is affordable, efficient, and widely applicable. Together, these features enable sTM-Seq to have wide-reaching clinical applications that will greatly improve turnaround rates for same-day procedures and allow clinicians to collect high-resolution data that can be used in a variety of patient settings. © 2019 by John Wiley & Sons, Inc.]]>
Wed, 31 Dec 1969 19:00:00 EST
Interactome mapping defines BRG1, a component of the SWI/SNF chromatin remodeling complex, as a new partner of the transcriptional regulator CTCF. Marino MM, Rega C, Russo R, Valletta M, Gentile MT, Esposito S, Baglivo I, De Feis I, Angelini C, Xiao T, Felsenfeld G, Chambery A, Pedone PV
J Biol Chem (Jan 2019)

The highly conserved zinc finger CCCTC-binding factor (CTCF) regulates genomic imprinting and gene expression by acting as a transcriptional activator or repressor of promoters and insulator of enhancers. The multiple functions of CTCF are accomplished by co-association with other protein partners and are dependent on genomic context and tissue specificity. Despite the critical role of CTCF in the organization of genome structure, to date, only a subset of CTCF interaction partners have been identified. Here we present a large-scale identification of CTCF-binding partners using affinity purification and high-resolution LC-MS/MS analysis. In addition to functional enrichment of specific protein families such as the ribosomal proteins and the DEAD box helicases, we identified novel high-confidence CTCF interactors that provide a still unexplored biochemical context for CTCF's multiple functions. One of the newly validated CTCF interactors is BRG1, the major ATPase subunit of the chromatin remodeling complex SWI/SNF, establishing a relationship between two master regulators of genome organization. This work significantly expands the current knowledge of the human CTCF interactome and represents an important resource to direct future studies aimed at uncovering molecular mechanisms modulating CTCF pleiotropic functions throughout the genome.]]>
Wed, 31 Dec 1969 19:00:00 EST
Link between depression and cardiovascular diseases due to epigenomics and proteomics: Focus on energy metabolism. Kahl KG, Stapel B, Frieling H
Prog Neuropsychopharmacol Biol Psychiatry (Mar 2019)

Major depression is the most common mental disorder and a leading cause of years lived with disability. In addition to the burden attributed to depressive symptoms and reduced daily life functioning, people with major depression are at increased risk of premature mortality, particularly due to cardiovascular diseases. Several studies point to a bi-directional relation between major depression and cardiovascular diseases, thereby indicating that both diseases may share common pathophysiological pathways. These include lifestyle factors (e.g. physical activity, smoking behavior), dysfunctions of endocrine systems (e.g. hypothalamus-pituitary adrenal axis), and a dysbalance of pro- and anti-inflammatory factors. Furthermore, recent research point to the role of epigenomic and proteomic factors, that are reviewed here with a particular focus on the mitochondrial energy metabolism.]]>
Wed, 31 Dec 1969 19:00:00 EST
Paediatrician's guide to epigenetics. Byrne L, Drake AJ
Arch Dis Child (Jan 2019)

Epigenetic regulation of gene expression is critical for normal development. Dysregulation of the epigenome can lead to the development and progression of a number of diseases relevant to paediatricians, including disorders of genomic imprinting and malignancies. It has long been recognised that early life events have implications for future disease risk, and epigenetic modifications may play a role in this, although further high-quality research is needed to better understand the underlying mechanisms. Research in the field of epigenetics will contribute to a greater understanding of growth, development and disease; however, paediatricians need to be able to interpret such research critically, in order to use the potential advances brought about through epigenetic studies while appreciating their limitations.]]>
Wed, 31 Dec 1969 19:00:00 EST
Integration of microbiology, molecular pathology, and epidemiology: a new paradigm to explore the pathogenesis of microbiome-driven neoplasms. Hamada T, Nowak JA, Milner DA, Song M, Ogino S
J Pathol (Jan 2019)

Molecular pathological epidemiology (MPE) is an integrative transdisciplinary field that addresses heterogeneous effects of exogenous and endogenous factors (collectively termed "exposures"), including microorganisms, on disease occurrence and consequence utilising molecular pathological signatures of the disease. In parallel with the paradigm of precision medicine, findings from MPE research can provide aetiological insights into tailored strategies of disease prevention and treatment. Due to the availability of molecular pathological tests on tumours, the MPE approach has been utilised predominantly in research on cancers including breast, lung, prostate, and colorectal carcinomas. Mounting evidence indicates that the microbiome (inclusive of viruses, bacteria, fungi, and parasites) plays an important role in a variety of human diseases including neoplasms. An alteration of the microbiome may be not only a cause of neoplasia but also an informative biomarker that indicates or mediates the association of an epidemiological exposure with health conditions and outcomes. To adequately educate and train investigators in this emerging area, we herein propose the integration of microbiology into the MPE model (termed "microbiology-MPE"), which can improve our understanding of the complex interactions of environment, tumour cells, the immune system, and microbes in the tumour microenvironment during the carcinogenic process. Using this approach, we can examine how lifestyle factors, dietary patterns, medications, environmental exposures, and germline genetics influence cancer development and progression through impacting the microbial communities in the human body. Further integration of other disciplines (e.g. pharmacology, immunology, nutrition) into microbiology-MPE would expand this developing research frontier. With the advent of high-throughput next-generation sequencing technologies, researchers now have increasing access to large-scale metagenomics as well as other omics data (e.g. genomics, epigenomics, proteomics, and metabolomics) in population-based research. The integrative field of microbiology-MPE will open new opportunities for personalised medicine and public health.]]>
Wed, 31 Dec 1969 19:00:00 EST
How does homeostasis happen? Integrative physiologic, systems biologic, and evolutionary perspectives. Goldstein DS
Am J Physiol Regul Integr Comp Physiol (Jan 2019)

Homeostasis is a founding principle of integrative physiology. In current systems biology, however, homeostasis seems almost invisible. Is homeostasis a key goal driving body processes, or is it an emergent mechanistic fact? In this perspective piece I propose that the integrative physiologic and systems biologic viewpoints about homeostasis reflect different epistemologies-different philosophies of knowledge. Integrative physiology is concept-driven. It attempts to explain biological phenomena by continuous formation of theories that experimentation or observation can test. In integrative physiology, "function" refers to goals or purposes. Systems biology is data-driven. It explains biological phenomena in terms of "omics"-genomics, gene expression, epigenomics, proteomics, metabolomics-depicts the data in computer models of complex cascades or networks, and makes predictions from the models. In systems biology "function" refers more to mechanisms than to goals. The integrative physiologist emphasizes homeostasis of internal variables such as pCO2 and blood pressure. The systems biologist views these emphases as teleologic and unparsimonious in that the "regulated variable" (e.g., arterial pCO2 and blood pressure) and the "regulator" (e.g., the "carbistat" and "barostat") are unobservable constructs. The integrative physiologist views systems biologic explanations as not really explanations but descriptions that cannot account for phenomena we humans believe exist although they cannot be observed directly, such as feelings and, ultimately, the conscious mind. This essay reviews the history of the two epistemologies, emphasizing autonomic neuroscience. I predict rapprochement of integrative physiology with systems biology. The resolution will avoid teleological purposiveness, transcend pure mechanism, and incorporate adaptiveness in evolution-"Darwinian medicine."]]>
Wed, 31 Dec 1969 19:00:00 EST
Evolution of viviparity in mammals: what genomic imprinting tells us about mammalian placental evolution. Kaneko-Ishino T, Ishino F
Reprod Fertil Dev (Jan 2019)

Genomic imprinting is an epigenetic mechanism of regulating parent-of-origin-specific monoallelic expression of imprinted genes in viviparous therian mammals such as eutherians and marsupials. In this review we discuss several issues concerning the relationship between mammalian viviparity and genomic imprinting, as well as the domestication of essential placental genes: why has the genomic imprinting mechanism been so widely conserved despite the evident developmental disadvantages originating from monoallelic expression? How have genomic imprinted regions been established in the course of mammalian evolution? What drove the evolution of mammalian viviparity and how have genomic imprinting and domesticated genes contributed to this process? In considering the regulatory mechanism of imprinted genes, reciprocal expression of paternally and maternally expressed genes (PEGs and MEGs respectively) and the presence of several essential imprinted genes for placental formation and maintenance, it is likely that complementary, thereby monoallelic, expression of PEGs and MEGs is an evolutionary trade-off for survival. The innovation in novel imprinted regions was associated with the emergence of imprinting control regions, suggesting that genomic imprinting arose as a genome defence mechanism against the insertion of exogenous DNA. Mammalian viviparity emerged in the period when the atmospheric oxygen concentration was the lowest (~12%) during the last 550 million years (the Phanerozoic eon), implying this low oxygen concentration was a key factor in promoting mammalian viviparity as a response to a major evolutionary pressure. Because genomic imprinting and gene domestication from retrotransposons or retroviruses are effective measures of changing genomic function in therian mammals, they are likely to play critical roles in the emergence of viviparity for longer gestation periods.]]>
Wed, 31 Dec 1969 19:00:00 EST
Global DNA methylation remodeling during direct reprogramming of fibroblasts to neurons. Luo C, Lee QY, Wapinski O, Castanon R, Nery JR, Mall M, Kareta MS, Cullen SM, Goodell MA, Chang HY, Wernig M, Ecker JR
Elife (Jan 2019)

Direct reprogramming of fibroblasts to neurons induces widespread cellular and transcriptional reconfiguration. Here, we characterized global epigenomic changes during the direct reprogramming of mouse fibroblasts to neurons using whole-genome base-resolution DNA methylation (mC) sequencing. We found that the pioneer transcription factor Ascl1 alone is sufficient for inducing the uniquely neuronal feature of non-CG methylation (mCH), but co-expression of Brn2 and Mytl1 was required to establish a global mCH pattern reminiscent of mature cortical neurons. Ascl1 alone induced promoter CG methylation (mCG) of fibroblast specific genes, while BAM overexpression additionally targets a competing myogenic program and directs a more faithful conversion to neuronal cells. Ascl1 induces local demethylation at its binding sites. Surprisingly, co-expression with Brn2 and Mytl1 inhibited the ability of Ascl1 to induce demethylation, suggesting a contextual regulation of transcription factor - epigenome interaction. Finally, we found that de novo methylation by DNMT3A is required for efficient neuronal reprogramming.]]>
Wed, 31 Dec 1969 19:00:00 EST
KUNO-Kids birth cohort study: rationale, design, and cohort description. Brandstetter S, Toncheva AA, Niggel J, Wolff C, Gran S, Seelbach-Göbel B, Apfelbacher C, Melter M, Kabesch M,  
Mol Cell Pediatr (Jan 2019)

Birth cohort studies can contribute substantially to the understanding of health and disease - in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various aspects of child health, using novel omics technologies in a systems medicine approach.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genomic imprinting disorders: lessons on how genome, epigenome and environment interact. Monk D, Mackay DJG, Eggermann T, Maher ER, Riccio A
Nat Rev Genet (Jan 2019)

Genomic imprinting, the monoallelic and parent-of-origin-dependent expression of a subset of genes, is required for normal development, and its disruption leads to human disease. Imprinting defects can involve isolated or multilocus epigenetic changes that may have no evident genetic cause, or imprinting disruption can be traced back to alterations of cis-acting elements or trans-acting factors that control the establishment, maintenance and erasure of germline epigenetic imprints. Recent insights into the dynamics of the epigenome, including the effect of environmental factors, suggest that the developmental outcomes and heritability of imprinting disorders are influenced by interactions between the genome, the epigenome and the environment in germ cells and early embryos.]]>
Wed, 31 Dec 1969 19:00:00 EST
The origins of genomic imprinting in mammals. Edwards CA, Takahashi N, Corish JA, Ferguson-Smith AC
Reprod Fertil Dev (Jan 2019)

Genomic imprinting is a process that causes genes to be expressed according to their parental origin. Imprinting appears to have evolved gradually in two of the three mammalian subclasses, with no imprinted genes yet identified in prototheria and only six found to be imprinted in marsupials to date. By interrogating the genomes of eutherian suborders, we determine that imprinting evolved at the majority of eutherian specific genes before the eutherian radiation. Theories considering the evolution of imprinting often relate to resource allocation and recently consider maternal-offspring interactions more generally, which, in marsupials, places a greater emphasis on lactation. In eutherians, the imprint memory is retained at least in part by zinc finger protein 57 (ZFP57), a Kruppel associated box (KRAB) zinc finger protein that binds specifically to methylated imprinting control regions. Some imprints are less dependent on ZFP57invivo and it may be no coincidence that these are the imprints that are found in marsupials. Because marsupials lack ZFP57, this suggests another more ancestral protein evolved to regulate imprints in non-eutherian subclasses, and contributes to imprinting control in eutherians. Hence, understanding the mechanisms acting at imprinting control regions across mammals has the potential to provide valuable insights into our understanding of the origins and evolution of genomic imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Transcription alterations of KCNQ1 associated with imprinted methylation defects in the Beckwith-Wiedemann locus. Valente FM, Sparago A, Freschi A, Hill-Harfe K, Maas SM, Frints SGM, Alders M, Pignata L, Franzese M, Angelini C, Carli D, Mussa A, Gazzin A, Gabbarini F, Acurzio B, Ferrero GB, Bliek J, Williams CA, Riccio A, Cerrato F
Genet Med (Jan 2019)

Beckwith-Wiedemann syndrome (BWS) is a developmental disorder caused by dysregulation of the imprinted gene cluster of chromosome 11p15.5 and often associated with loss of methylation (LOM) of the imprinting center 2 (IC2) located in KCNQ1 intron 10. To unravel the etiological mechanisms underlying these epimutations, we searched for genetic variants associated with IC2 LOM.]]>
Wed, 31 Dec 1969 19:00:00 EST
Integrative analysis of genome-wide association study and chromosomal enhancer maps identified brain region related pathways associated with ADHD. Cheng B, Du Y, Wen Y, Zhao Y, He A, Ding M, Fan Q, Li P, Liu L, Liang X, Guo X, Zhang F, Ma X
Compr Psychiatry (Jan 2019)

Attention deficit/hyperactivity disorder (ADHD) is among the most common childhood onset psychiatric behavioral disorders, and the pathogenesis of ADHD is still unclear. Utilizing the latest genome wide association studies (GWAS) data and enhancer map, we explored the brain region related biological pathways associated with ADHD. The GWAS summary data of ADHD was driven from a published study, involving 20,183 ADHD cases and 35,191 healthy controls. The brain-related enhancer map was collected from ENCODE and Roadmap Epigenomics (ENCODE + Roadmap) including 489,581 enhancers. Firstly, the chromosomal enhancer maps of four brain regions were aligned with the ADHD GWAS summary data in order to obtain enhancer SNPs. Then the significant enhancers SNPs were subjected to the gene set enrichment analysis (GSEA) for identifying ADHD associated gene sets. A total of 866 pathways and 4 brain tissues were analyzed in this study. We detected several candidate genes for ADHD, such as AHI1, ALG2 and DNM1. We also detected several candidate biological pathways associated with ADHD, such as Reactome SEMA4D in semaphorin signaling and Reactome NCAM1 interactions. Our findings may provide a novel insight into the complex genetic mechanism of ADHD.]]>
Wed, 31 Dec 1969 19:00:00 EST