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
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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