Postmortem human brain genomics in neuropsychiatric disorders — how far can we go?
Open accessAbstract
Large-scale collection of postmortem human brain tissue and subsequent genomic data generation has become a useful approach for better identifying etiological factors contributing to neuropsychiatric disorders. In particular, studying genetic risk variants in non-psychiatric controls can identify biological mechanisms of risk free from confounding factors related to epiphenomena of illness. While the field has begun moving towards cell type-specific analyses, homogenate brain tissue with accompanying cellular profiles, can still identify useful hypotheses for more focused experiments, particularly when the dysregulated cell types are unknown. Technological advances, larger sample sizes, and focused research questions can continue to further leverage postmortem human brain research to better identify and understand the molecular etiology of neuropsychiatric disorders.
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Few studies have examined the human brain for cell-type-specific differences in transcriptional states as a result of tissue handling or acute pre/postmortem processes.
“However, few studies have examined the human brain for cell-type-specific differences in transcriptional states as a result of tissue handling or acute pre/postmortem processes12, and to our knowledge none have done so in a cell-type-specific manner using snRNA-seq.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [12]
The ‘Functional genomics in the human brain’ section says agonal state and the time between death and tissue processing can affect observed gene expression. ‘Moving towards interrogating individual cell populations’ describes cell-type-specific analysis of postmortem human brain as a challenge. Neither passage establishes that few studies have examined cell-type-specific transcriptional responses to tissue handling or acute pre/postmortem processes. (LLM, conf=0.82)
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- Authors
- Jaffe, A. E.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Jaffe, Andrew E
- ORCID
- Jaffe, Andrew E
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 36
- Pages
- 107-111
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC4857188
- OpenAlex
- W2193750816
- Cited by
- 19
- References
- 54
- Citations by year
- 2026: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R21MH105853)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- human postmortem brain, neuropsychiatric disorders, genetic risk variants, etiology, molecular etiology
- MeSH terms
- Autism Spectrum Disorder, Autopsy, Mental Disorders, Bipolar Disorder, Brain, Depressive Disorder, Major, Major Depressive Disorder, Humans, Schizophrenia, Gene Expression Profiling, Genomics, Epigenesis, Genetic
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