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- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 2. |
- Lopes, F. L., et al.
(författare)
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Polygenic risk for anxiety influences anxiety comorbidity and suicidal behavior in bipolar disorder
- 2020
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is often comorbid with anxiety, which is itself associated with poorer clinical outcomes, including suicide. A better etiologic understanding of this comorbidity could inform diagnosis and treatment. The present study aims to test whether comorbid anxiety in bipolar disorder reflects shared genetic risk factors. We also sought to assess the contribution of genetic risk for anxiety to suicide attempts in bipolar disorder. Polygenic risk scores (PRS) were calculated from published genome-wide association studies of samples of controls and cases with anxiety (n = 83,566) or bipolar disorder (n = 51,710), then scored in independent target samples (totaln = 3369) of individuals with bipolar disorder who reported or denied lifetime anxiety disorders or suicidal attempts in research interviews. Participants were recruited from clinical and nonclinical settings and genotyped for common genetic variants. The results show that polygenic risk for anxiety was associated with comorbid anxiety disorders and suicide attempts in bipolar disorder, while polygenic risk for bipolar disorder was not associated with any of these variables. Our findings point out that comorbid anxiety disorders in bipolar disorder reflect a dual burden of bipolar and anxiety-related genes; the latter may also contribute to suicide attempts. Clinical care that recognizes and addresses this dual burden may help improve outcomes in people living with comorbid bipolar and anxiety disorders.
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