The genetic architecture of the human thalamus and its overlap with ten common brain disorders.
Brain Diseases
/ classification
Brain Mapping
/ methods
Cerebral Cortex
/ diagnostic imaging
Genetic Loci
/ genetics
Genetic Predisposition to Disease
/ genetics
Genome, Human
/ genetics
Genome-Wide Association Study
/ methods
Humans
Linkage Disequilibrium
Magnetic Resonance Imaging
/ methods
Mental Disorders
/ classification
Polymorphism, Single Nucleotide
Quantitative Trait Loci
/ genetics
Thalamic Nuclei
/ diagnostic imaging
Thalamus
/ diagnostic imaging
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 05 2021
18 05 2021
Historique:
received:
02
10
2020
accepted:
16
04
2021
entrez:
19
5
2021
pubmed:
20
5
2021
medline:
16
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34006833
doi: 10.1038/s41467-021-23175-z
pii: 10.1038/s41467-021-23175-z
pmc: PMC8131358
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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