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- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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- Ingason, A, et al.
(författare)
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Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia
- 2015
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5, s. e656-
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Tidskriftsartikel (refereegranskat)abstract
- Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.
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- Legge, SE, et al.
(författare)
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Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia
- 2018
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 23:1, s. 162-163
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Tidskriftsartikel (refereegranskat)abstract
- Correction to: Molecular Psychiatry (2017) 22: 1502-1508; advance online publication, 12 July 2017; doi: 10.1038/mp.2016.97 In the first paragraph of the Results section and Figure 1, the authors incorrectly referred to the finding of SNP rs77897117. The correct SNP is rs77897177. The corrected figure appears in previous page.
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