The genetic architecture of the human thalamus and its overlap with ten common brain disorders
Autor: | Shahram Bahrami, Torbjørn Elvsåshagen, Lars T. Westlye, Tobias Kaufmann, Vinod Kumar, Oleksandr Frei, Dennis van der Meer, Olav B. Smeland, Alexey A. Shadrin, Ole A. Andreassen |
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Přispěvatelé: | RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Linkage disequilibrium CHROMATIN-STATE DISCOVERY THALAMOCORTICAL DYSCONNECTIVITY General Physics and Astronomy Genome-wide association study Linkage Disequilibrium 0302 clinical medicine Thalamus Genetics research SCHIZOPHRENIA Cerebral Cortex Brain Diseases Brain Mapping Multidisciplinary Mental Disorders Brain Magnetic Resonance Imaging Schizophrenia Thalamic Nuclei EXPRESSION Science Quantitative Trait Loci Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Neuroimaging medicine Humans Genetic Predisposition to Disease GENOME-WIDE ASSOCIATION METAANALYSIS IDENTIFICATION Genome Human General Chemistry medicine.disease RISK LOCI Human genetics Genetic architecture INDIVIDUALS 030104 developmental biology Genetic Loci PROJECTIONS Diseases of the nervous system Psychiatric disorders Neuroscience 030217 neurology & neurosurgery Neurological disorders Genome-Wide Association Study |
Zdroj: | Nature Communications, 12(1):2909. Nature Publishing Group Nature Communications, Vol 12, Iss 1, Pp 1-9 (2021) Nature Communications |
ISSN: | 2041-1723 |
Popis: | The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identify 55 lead single nucleotide polymorphisms (SNPs) within 42 genetic loci and 391 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5173) 53 out of the 55 lead SNPs of the discovery sample show the same effect direction (sign test, P = 8.6e-14). We map the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and find overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders reveal shared variants for all disorders. Together, these analyses identify genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders. Differences in thalamic structure have been observed in several psychiatric disorders, but the genetic overlap has not been explored. Here, the authors perform a genome-wide association study on thalamic nuclei volume and find genetic loci in common between thalamic volumes and brain disorders. |
Databáze: | OpenAIRE |
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