Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity
Abstract Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brai...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55611-1 |
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| author | Shuyang Yao Arvid Harder Fahimeh Darki Yu-Wei Chang Ang Li Kasra Nikouei Giovanni Volpe Johan N. Lundström Jian Zeng Naomi R. Wray Yi Lu Patrick F. Sullivan Jens Hjerling-Leffler |
| author_facet | Shuyang Yao Arvid Harder Fahimeh Darki Yu-Wei Chang Ang Li Kasra Nikouei Giovanni Volpe Johan N. Lundström Jian Zeng Naomi R. Wray Yi Lu Patrick F. Sullivan Jens Hjerling-Leffler |
| author_sort | Shuyang Yao |
| collection | DOAJ |
| description | Abstract Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability. Using functional MRI connectivity, we further confirmed the significance of the central and lateral amygdala, hippocampal body, and prefrontal cortex in distinguishing schizophrenia cases from controls. Our findings underscore the value of single-cell transcriptomics in understanding the polygenicity of psychiatric disorders and suggest a promising alignment of genomic, transcriptomic, and brain imaging modalities for identifying common biological targets. |
| format | Article |
| id | doaj-art-6d67c95fc646426d94aef8c8ddfb2929 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-6d67c95fc646426d94aef8c8ddfb29292025-01-05T12:38:46ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-024-55611-1Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivityShuyang Yao0Arvid Harder1Fahimeh Darki2Yu-Wei Chang3Ang Li4Kasra Nikouei5Giovanni Volpe6Johan N. Lundström7Jian Zeng8Naomi R. Wray9Yi Lu10Patrick F. Sullivan11Jens Hjerling-Leffler12Department of Medical Biochemistry and Biophysics, Karolinska InstitutetDepartment of Medical Biochemistry and Biophysics, Karolinska InstitutetDepartment of Clinical Neuroscience, Karolinska InstitutetDepartment of Physics, University of GothenburgInstitute for Molecular Bioscience, University of QueenslandDepartment of Medical Biochemistry and Biophysics, Karolinska InstitutetDepartment of Physics, University of GothenburgDepartment of Clinical Neuroscience, Karolinska InstitutetInstitute for Molecular Bioscience, University of QueenslandInstitute for Molecular Bioscience, University of QueenslandDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Biochemistry and Biophysics, Karolinska InstitutetAbstract Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability. Using functional MRI connectivity, we further confirmed the significance of the central and lateral amygdala, hippocampal body, and prefrontal cortex in distinguishing schizophrenia cases from controls. Our findings underscore the value of single-cell transcriptomics in understanding the polygenicity of psychiatric disorders and suggest a promising alignment of genomic, transcriptomic, and brain imaging modalities for identifying common biological targets.https://doi.org/10.1038/s41467-024-55611-1 |
| spellingShingle | Shuyang Yao Arvid Harder Fahimeh Darki Yu-Wei Chang Ang Li Kasra Nikouei Giovanni Volpe Johan N. Lundström Jian Zeng Naomi R. Wray Yi Lu Patrick F. Sullivan Jens Hjerling-Leffler Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity Nature Communications |
| title | Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity |
| title_full | Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity |
| title_fullStr | Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity |
| title_full_unstemmed | Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity |
| title_short | Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity |
| title_sort | connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity |
| url | https://doi.org/10.1038/s41467-024-55611-1 |
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