Amygdala and anterior cingulate transcriptomes from individuals with bipolar disorder reveal downregulated neuroimmune and synaptic pathways.

Autor:	Zandi PP; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. pzandi1@jhu.edu.; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. pzandi1@jhu.edu., Jaffe AE; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; The Lieber Institute for Brain Development, Baltimore, MD, USA.; Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA.; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA., Goes FS; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Burke EE; The Lieber Institute for Brain Development, Baltimore, MD, USA., Collado-Torres L; The Lieber Institute for Brain Development, Baltimore, MD, USA.; Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA., Huuki-Myers L; The Lieber Institute for Brain Development, Baltimore, MD, USA., Seyedian A; The Lieber Institute for Brain Development, Baltimore, MD, USA., Lin Y; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Seifuddin F; The National Heart, Lung and Blood Institute, the National Institute of Health, Bethesda, MD, USA., Pirooznia M; The National Heart, Lung and Blood Institute, the National Institute of Health, Bethesda, MD, USA., Ross CA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Kleinman JE; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; The Lieber Institute for Brain Development, Baltimore, MD, USA., Weinberger DR; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; The Lieber Institute for Brain Development, Baltimore, MD, USA.; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Hyde TM; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. thomas.hyde@libd.org.; The Lieber Institute for Brain Development, Baltimore, MD, USA. thomas.hyde@libd.org.; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA. thomas.hyde@libd.org.
Jazyk:	angličtina
Zdroj:	Nature neuroscience [Nat Neurosci] 2022 Mar; Vol. 25 (3), pp. 381-389. Date of Electronic Publication: 2022 Mar 07.
DOI:	10.1038/s41593-022-01024-6
Abstrakt:	Recent genetic studies have identified variants associated with bipolar disorder (BD), but it remains unclear how brain gene expression is altered in BD and how genetic risk for BD may contribute to these alterations. Here, we obtained transcriptomes from subgenual anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with BD and neurotypical controls, including 511 total samples from 295 unique donors. We examined differential gene expression between cases and controls and the transcriptional effects of BD-associated genetic variants. We found two coexpressed modules that were associated with transcriptional changes in BD: one enriched for immune and inflammatory genes and the other with genes related to the postsynaptic membrane. Over 50% of BD genome-wide significant loci contained significant expression quantitative trait loci (QTL) (eQTL), and these data converged on several individual genes, including SCN2A and GRIN2A. Thus, these data implicate specific genes and pathways that may contribute to the pathology of BP. (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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