Genetic implication of prenatal GABAergic and cholinergic neuron development in susceptibility to schizophrenia DOI Creative Commons
Darren Cameron,

Ngoc‐Nga Vinh,

Parinda Prapaiwongs

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 14, 2023

Abstract Background The ganglionic eminences are fetal-specific structures that give rise to gamma- aminobutyric acid (GABA)- and acetylcholine- releasing neurons of the forebrain. Given evidence for GABAergic cholinergic disturbances in schizophrenia, as well an early neurodevelopmental component disorder, we tested potential involvement developing cells mediating genetic risk condition. Study Design We combined data from a recent large-scale genome-wide association study schizophrenia with single cell RNA sequencing human test enrichment variation genes high expression specificity particular populations within these structures. additionally performed nuclei Assay Transposase-Accessible Chromatin Sequencing (snATAC-Seq) map regulatory genomic regions operating individual eminences, using common variant liability functionally annotate non-coding variants associated disorder. Results Schizophrenia was enriched neuron predicted form dopamine D1 D2 receptor expressing medium spiny striatum, cortical somatostatin-positive interneurons, calretinin-positive neurons. Consistent findings, also concentrated sequence mapped neuronal eminences. Conclusions Our provides role prenatal development later susceptibility schizophrenia.

Language: Английский

Genetic implication of prenatal GABAergic and cholinergic neuron development in susceptibility to schizophrenia DOI Creative Commons
Darren Cameron,

Ngoc‐Nga Vinh,

Parinda Prapaiwongs

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 14, 2023

Abstract Background The ganglionic eminences are fetal-specific structures that give rise to gamma- aminobutyric acid (GABA)- and acetylcholine- releasing neurons of the forebrain. Given evidence for GABAergic cholinergic disturbances in schizophrenia, as well an early neurodevelopmental component disorder, we tested potential involvement developing cells mediating genetic risk condition. Study Design We combined data from a recent large-scale genome-wide association study schizophrenia with single cell RNA sequencing human test enrichment variation genes high expression specificity particular populations within these structures. additionally performed nuclei Assay Transposase-Accessible Chromatin Sequencing (snATAC-Seq) map regulatory genomic regions operating individual eminences, using common variant liability functionally annotate non-coding variants associated disorder. Results Schizophrenia was enriched neuron predicted form dopamine D1 D2 receptor expressing medium spiny striatum, cortical somatostatin-positive interneurons, calretinin-positive neurons. Consistent findings, also concentrated sequence mapped neuronal eminences. Conclusions Our provides role prenatal development later susceptibility schizophrenia.

Language: Английский

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