دورية أكاديمية
أعرض في EDS

Identification of brain cell types underlying genetic association with word reading and correlated traits.

التفاصيل البيبلوغرافية
العنوان: Identification of brain cell types underlying genetic association with word reading and correlated traits.
المؤلفون: Price KM; Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON, Canada.; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.; Department of Physiology, University of Toronto, Toronto, ON, Canada., Wigg KG; Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON, Canada., Nigam A; Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Feng Y; Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON, Canada., Blokland K; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada., Wilkinson M; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada., Kerr EN; Department of Psychology, Hospital for Sick Children, Toronto, ON, Canada.; Department of Pediatrics, University of Toronto, Toronto, ON, Canada., Guger SL; Department of Psychology, Hospital for Sick Children, Toronto, ON, Canada., Lovett MW; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.; Department of Pediatrics, University of Toronto, Toronto, ON, Canada., Strug LJ; Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.; Departments of Statistical Sciences and Computer Science, Faculty of Arts and Science and Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada., Tripathy SJ; Department of Physiology, University of Toronto, Toronto, ON, Canada.; Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada., Barr CL; Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON, Canada. Cathy.Barr@uhn.ca.; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada. Cathy.Barr@uhn.ca.; Department of Physiology, University of Toronto, Toronto, ON, Canada. Cathy.Barr@uhn.ca.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Cathy.Barr@uhn.ca.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Cathy.Barr@uhn.ca.
المصدر: Molecular psychiatry [Mol Psychiatry] 2023 Apr; Vol. 28 (4), pp. 1719-1730. Date of Electronic Publication: 2023 Feb 07.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-
مواضيع طبية MeSH: Dyslexia*/genetics , Attention Deficit Disorder with Hyperactivity*/genetics, Adult ; Humans ; Reading ; Genome-Wide Association Study/methods ; Brain ; Cognition
مستخلص: Neuroimaging studies implicate multiple cortical regions in reading ability/disability. However, the neural cell types integral to the reading process are unknown. To contribute to this gap in knowledge, we integrated genetic results from genome-wide association studies for word reading (n = 5054) with gene expression datasets from adult/fetal human brain. Linkage disequilibrium score regression (LDSC) suggested that variants associated with word reading were enriched in genes expressed in adult excitatory neurons, specifically layer 5 and 6 FEZF2 expressing neurons and intratelencephalic (IT) neurons, which express the marker genes LINC00507, THEMIS, or RORB. Inhibitory neurons (VIP, SST, and PVALB) were also found. This finding was interesting as neurometabolite studies previously implicated excitatory-inhibitory imbalances in the etiology of reading disabilities (RD). We also tested traits that shared genetic etiology with word reading (previously determined by polygenic risk scores): attention-deficit/hyperactivity disorder (ADHD), educational attainment, and cognitive ability. For ADHD, we identified enrichment in L4 IT adult excitatory neurons. For educational attainment and cognitive ability, we confirmed previous studies identifying multiple subclasses of adult cortical excitatory and inhibitory neurons, as well as astrocytes and oligodendrocytes. For educational attainment and cognitive ability, we also identified enrichment in multiple fetal cortical excitatory and inhibitory neurons, intermediate progenitor cells, and radial glial cells. In summary, this study supports a role of excitatory and inhibitory neurons in reading and excitatory neurons in ADHD and contributes new information on fetal cell types enriched in educational attainment and cognitive ability, thereby improving our understanding of the neurobiological basis of reading/correlated traits.
(© 2023. The Author(s).)
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معلومات مُعتمدة: MOP-133440 Canada CIHR; PJT-180419 Canada CIHR
تواريخ الأحداث: Date Created: 20230208 Date Completed: 20230526 Latest Revision: 20230528
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10208966
DOI: 10.1038/s41380-023-01970-y
PMID: 36750735
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5578
DOI:10.1038/s41380-023-01970-y