Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD.

Humans Autism Spectrum Disorder / genetics Cerebral Cortex / metabolism Neurons / metabolism RNA / analysis Transcriptome / genetics Autopsy Sequence Analysis, RNA Primary Visual Cortex / metabolism Neuroglia / metabolism Genetic Variation

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
Nov 2022
Historique:
received: 17 12 2020
accepted: 21 09 2022
pubmed: 4 11 2022
medline: 22 11 2022
entrez: 3 11 2022
Statut: ppublish

Résumé

Neuropsychiatric disorders classically lack defining brain pathologies, but recent work has demonstrated dysregulation at the molecular level, characterized by transcriptomic and epigenetic alterations

Identifiants

DOI: 10.1038/s41586-022-05377-7 PMID: 36323788 PMC: PMC9668748
pubmed: 36323788
doi: 10.1038/s41586-022-05377-7
pii: 10.1038/s41586-022-05377-7
pmc: PMC9668748
doi:

Substances chimiques

RNA 63231-63-0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

532-539

Subventions

Organisme : NIA NIH HHS
ID : RF1 AG071683
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH125252
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH094714
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH115746
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109912
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH106438
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG071683
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103557
Pays : United States
Organisme : NIMH NIH HHS
ID : F32 MH124337
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH121521
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH123922
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110927
Pays : United States

Informations de copyright

© 2022. The Author(s).

Références

Gandal, M. J. et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science 362, eaat8127 (2018).
pubmed: 30545856 pmcid: 6443102 doi: 10.1126/science.aat8127
Wu, Y. E., Parikshak, N. N., Belgard, T. G. & Geschwind, D. H. Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder. Nat. Neurosci. 19, 1463–1476 (2016).
pubmed: 27571009 pmcid: 5841760 doi: 10.1038/nn.4373
Sun, W. et al. Histone acetylome-wide association study of autism spectrum disorder. Cell 167, 1385–1397.e11 (2016).
pubmed: 27863250 doi: 10.1016/j.cell.2016.10.031
Voineagu, I. et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474, 380–384 (2011).
pubmed: 21614001 pmcid: 3607626 doi: 10.1038/nature10110
Parikshak, N. N. et al. Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature 540, 423–427 (2016).
pubmed: 27919067 pmcid: 7102905 doi: 10.1038/nature20612
Gandal, M. J. et al. Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 359, 693–697 (2018).
pubmed: 29439242 pmcid: 5898828 doi: 10.1126/science.aad6469
Sullivan, P. F. & Geschwind, D. H. Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders. Cell 177, 162–183 (2019).
pubmed: 30901538 pmcid: 6432948 doi: 10.1016/j.cell.2019.01.015
de la Torre-Ubieta, L., Won, H., Stein, J. L. & Geschwind, D. H. Advancing the understanding of autism disease mechanisms through genetics. Nat. Med. 22, 345–361 (2016).
pubmed: 27050589 pmcid: 5072455 doi: 10.1038/nm.4071
Ramaswami, G. et al. Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism. Nat. Commun. 11, 4873 (2020).
pubmed: 32978376 pmcid: 7519165 doi: 10.1038/s41467-020-18526-1
Walker, R. L. et al. Genetic control of expression and splicing in developing human brain informs disease mechanisms. Cell 179, 750–771.e22 (2019).
pubmed: 31626773 pmcid: 8963725 doi: 10.1016/j.cell.2019.09.021
Oldham, M. C. et al. Functional organization of the transcriptome in human brain. Nat. Neurosci. 11, 1271–1282 (2008).
pubmed: 18849986 pmcid: 2756411 doi: 10.1038/nn.2207
Bernard, A. et al. Transcriptional architecture of the primate neocortex. Neuron 73, 1083–1099 (2012).
pubmed: 22445337 pmcid: 3628746 doi: 10.1016/j.neuron.2012.03.002
Hawrylycz, M. J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012).
pubmed: 22996553 pmcid: 4243026 doi: 10.1038/nature11405
Amunts, K. & Zilles, K. Architectonic mapping of the human brain beyond Brodmann. Neuron 88, 1086–1107 (2015).
pubmed: 26687219 doi: 10.1016/j.neuron.2015.12.001
Klingler, E. et al. Temporal controls over inter-areal cortical projection neuron fate diversity. Nature 599, 453–457 (2021).
pubmed: 34754107 doi: 10.1038/s41586-021-04048-3
Fontanet, P. A., Ríos, A. S., Alsina, F. C., Paratcha, G. & Ledda, F. Pea3 transcription factors, Etv4 and Etv5, are required for proper hippocampal dendrite development and plasticity. Cereb. Cortex 28, 236–249 (2018).
pubmed: 27909004 doi: 10.1093/cercor/bhw372
Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinf. 9, 559 (2008).
doi: 10.1186/1471-2105-9-559
Zhang, B. & Horvath, S. A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol. 4, 17 (2005).
doi: 10.2202/1544-6115.1128
Langfelder, P., Luo, R., Oldham, M. C. & Horvath, S. Is my network module preserved and reproducible? PLoS Comput. Biol. 7, e1001057 (2011).
pubmed: 21283776 pmcid: 3024255 doi: 10.1371/journal.pcbi.1001057
Parikshak, N. N. et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell 155, 1008–1021 (2013).
pubmed: 24267887 pmcid: 3934107 doi: 10.1016/j.cell.2013.10.031
Grove, J. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431–444 (2019).
pubmed: 30804558 pmcid: 6454898 doi: 10.1038/s41588-019-0344-8
Abrahams, B. S. et al. SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs). Mol. Autism 4, 36 (2013).
pubmed: 24090431 pmcid: 3851189 doi: 10.1186/2040-2392-4-36
Hodge, R. D. et al. Conserved cell types with divergent features in human versus mouse cortex. Nature 573, 61–68 (2019).
pubmed: 31435019 pmcid: 6919571 doi: 10.1038/s41586-019-1506-7
Keller, D., Erö, C. & Markram, H. Cell densities in the mouse brain: a systematic review. Front. Neuroanat. 12, 83 (2018).
pubmed: 30405363 pmcid: 6205984 doi: 10.3389/fnana.2018.00083
Collins, C. E., Airey, D. C., Young, N. A., Leitch, D. B. & Kaas, J. H. Neuron densities vary across and within cortical areas in primates. Proc. Natl Acad. Sci. USA 107, 15927–15932 (2010).
pubmed: 20798050 pmcid: 2936588 doi: 10.1073/pnas.1010356107
Collins, C. E. et al. Cortical cell and neuron density estimates in one chimpanzee hemisphere. Proc. Natl Acad. Sci. USA 113, 740–745 (2016).
pubmed: 26729880 pmcid: 4725503 doi: 10.1073/pnas.1524208113
Cadwell, C. R., Bhaduri, A., Mostajo-Radji, M. A., Keefe, M. G. & Nowakowski, T. J. Development and arealization of the cerebral cortex. Neuron 103, 980–1004 (2019).
pubmed: 31557462 pmcid: 9245854 doi: 10.1016/j.neuron.2019.07.009
Wagstyl, K. et al. BigBrain 3D atlas of cortical layers: cortical and laminar thickness gradients diverge in sensory and motor cortices. PLoS Biol. 18, e3000678 (2020).
pubmed: 32243449 pmcid: 7159250 doi: 10.1371/journal.pbio.3000678
Luo, C. et al. Single nucleus multi-omics identifies human cortical cell regulatory genome diversity. Cell Genomics 2, 100106 (2022).
pubmed: 35419551 pmcid: 9004682 doi: 10.1016/j.xgen.2022.100107
Gupta, S. et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat. Commun. 5, 5748 (2014).
pubmed: 25494366 doi: 10.1038/ncomms6748
Diagnostic and Statistical Manual of Mental Disorders: DSM-5 (American Psychiatric Association, 2013).
Ecker, C. et al. Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder. Proc. Natl Acad. Sci. USA 110, 13222–13227 (2013).
pubmed: 23878213 pmcid: 3740833 doi: 10.1073/pnas.1221880110
Hilgetag, C. C., Beul, S. F., van Albada, S. J. & Goulas, A. An architectonic type principle integrates macroscopic cortico-cortical connections with intrinsic cortical circuits of the primate brain. Netw. Neurosci. 3, 905–923 (2019).
pubmed: 31637331 pmcid: 6777964 doi: 10.1162/netn_a_00100
Bhaduri, A. et al. An atlas of cortical arealization identifies dynamic molecular signatures. Nature 598, 200–204 (2021).
pubmed: 34616070 pmcid: 8494648 doi: 10.1038/s41586-021-03910-8
Patrick, E. et al. Deconvolving the contributions of cell-type heterogeneity on cortical gene expression. PLoS Comput. Biol. 16, e1008120 (2020).
pubmed: 32804935 pmcid: 7451979 doi: 10.1371/journal.pcbi.1008120
Arzalluz-Luque, Á. & Conesa, A. Single-cell RNAseq for the study of isoforms—how is that possible? Genome Biol. 19, 110 (2018).
pubmed: 30097058 pmcid: 6085759 doi: 10.1186/s13059-018-1496-z
Zhu, P. J. et al. Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome. Science 366, 843–849 (2019).
pubmed: 31727829 pmcid: 7299149 doi: 10.1126/science.aaw5185
Di Nardo, A. et al. Phenotypic screen with TSC-deficient neurons reveals heat-shock machinery as a druggable pathway for mTORC1 and reduced cilia. Cell Rep. 31, 107780 (2020).
pubmed: 32579942 pmcid: 7381997 doi: 10.1016/j.celrep.2020.107780
Demontis, D. et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat. Genet. 51, 63–75 (2019)
Lee, J. J. et al. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nat. Genet. 50, 1112–1121 (2018)
Savage, J. E. et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat. Genet. 50, 912–919 (2018).
Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes. Cell 173, 1705–1715.e16 (2018).
Wray, N. R. et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat. Genet. 50, 668–681 (2018).
Pardiñas, A. F. et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat. Genet. 50, 381–389 (2018).
Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat. Genet. 47, 979–986 (2015).
Andrews, S. et al. FastQC. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/ (2010).
Yates, A. D. et al. Ensembl 2020. Nucleic Acids Res. 48, D682–D688 (2020).
pubmed: 31691826
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886 doi: 10.1093/bioinformatics/bts635
Jun, G. et al. Detecting and estimating contamination of human DNA samples in sequencing and array-based genotype data. Am. J. Hum. Genet. 91, 839–848 (2012).
pubmed: 23103226 pmcid: 3487130 doi: 10.1016/j.ajhg.2012.09.004
Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011).
pubmed: 21816040 pmcid: 3163565 doi: 10.1186/1471-2105-12-323
Frankish, A. et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 47, D766–D773 (2019).
pubmed: 30357393 doi: 10.1093/nar/gky955
R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2020).
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
pubmed: 25605792 pmcid: 4402510 doi: 10.1093/nar/gkv007
Hansen, K. D., Irizarry, R. A. & Wu, Z. Removing technical variability in RNA-seq data using conditional quantile normalization. Biostatistics 13, 204–216 (2012).
pubmed: 22285995 pmcid: 3297825 doi: 10.1093/biostatistics/kxr054
Kuznetsova, A., Brockhoff, P. B. & Christensen, R. H. B. lmerTest package: tests in linear mixed effects models. J. Stat. Softw. https://doi.org/10.18637/jss.v082.i13 (2017).
Li, B. et al. Cumulus provides cloud-based data analysis for large-scale single-cell and single-nucleus RNA-seq. Nat. Methods 17, 793–798 (2020).
Velmeshev, D. et al. Single-cell genomics identifies cell type-specific molecular changes in autism. Science 364, 685–689 (2019).
pubmed: 31097668 pmcid: 7678724 doi: 10.1126/science.aav8130
Quinn, T. P. et al. A field guide for the compositional analysis of any-omics data. Gigascience 8, giz107 (2019).
pubmed: 31544212 pmcid: 6755255 doi: 10.1093/gigascience/giz107
He, L. et al. NEBULA is a fast negative binomial mixed model for differential or co-expression analysis of large-scale multi-subject single-cell data. Commun. Biol. 4, 629 (2021).
pubmed: 34040149 pmcid: 8155058 doi: 10.1038/s42003-021-02146-6
Wong, C. C. Y. et al. Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic autism in post-mortem human brain tissue. Hum. Mol. Genet. 28, 2201–2211 (2019).
pubmed: 31220268 pmcid: 6602383 doi: 10.1093/hmg/ddz052

Auteurs

Michael J Gandal (MJ)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. michael.gandal@pennmedicine.upenn.edu.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA. michael.gandal@pennmedicine.upenn.edu.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. michael.gandal@pennmedicine.upenn.edu.
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. michael.gandal@pennmedicine.upenn.edu.
Lifespan Brain Institute at Penn Medicine and The Children's Hospital of Philadelphia, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. michael.gandal@pennmedicine.upenn.edu.
ORCID: 0000-0001-5800-5128

Jillian R Haney (JR)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Brie Wamsley (B)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Chloe X Yap (CX)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.
Institute for Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia.
ORCID: 0000-0002-1788-2842

Sepideh Parhami (S)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Prashant S Emani (PS)

Computational Biology & Bioinformatics Program, Yale University, New Haven, CT, USA.
ORCID: 0000-0002-3091-5231

Nathan Chang (N)

Computational Biology & Bioinformatics Program, Yale University, New Haven, CT, USA.

George T Chen (GT)

Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
ORCID: 0000-0002-1342-0835

Gil D Hoftman (GD)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Diego de Alba (D)

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Gokul Ramaswami (G)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Christopher L Hartl (CL)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Arjun Bhattacharya (A)

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Chongyuan Luo (C)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Ting Jin (T)

Waisman Center and Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.

Daifeng Wang (D)

Waisman Center and Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.
ORCID: 0000-0001-9190-3704

Riki Kawaguchi (R)

Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Diana Quintero (D)

Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Jing Ou (J)

Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Ye Emily Wu (YE)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
ORCID: 0000-0001-8052-1073

Neelroop N Parikshak (NN)

Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Vivek Swarup (V)

Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.

T Grant Belgard (TG)

The Bioinformatics CRO, Niceville, FL, USA.
ORCID: 0000-0002-6962-7894

Mark Gerstein (M)

Computational Biology & Bioinformatics Program, Yale University, New Haven, CT, USA.

Bogdan Pasaniuc (B)

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
ORCID: 0000-0002-0227-2056

Daniel H Geschwind (DH)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. dhg@mednet.ucla.edu.
Center for Autism Research and Treatment, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA. dhg@mednet.ucla.edu.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. dhg@mednet.ucla.edu.
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. dhg@mednet.ucla.edu.
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. dhg@mednet.ucla.edu.
ORCID: 0000-0003-2896-3450

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Trouble du spectre autistique › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Cellules › Neurones › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Sciences sociales › Criminologie › Sciences légales › Médecine légale › Autopsie › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Cortex sensorimoteur › Cortex visuel › Cortex visuel primaire › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Cellules › Névroglie › Broad transcriptomic dysregulation occurs...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Broad transcriptomic dysregulation occurs...