Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders
Maria José González,
Susana Gil Flores,
Francisco J. Cabaleiro Fabeiro,
Francisco del Río Noriega,
Fermin Perez Perez,
Jesus Haro González,
Guillermo Orozco Diaz,
Yolanda de Diego-Otero,
Jerome C Foo,
Stephanie H Witt,
Bipolar Disorder Working Group of the Psychiatric Genomics Consortium,
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,
Andreas J. Forstner,
Markus M Noethen,
Posted 12 Nov 2018
bioRxiv DOI: 10.1101/468975 (published DOI: 10.1038/s41380-019-0558-2)
Posted 12 Nov 2018
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
- Downloaded 517 times
- Download rankings, all-time:
- Site-wide: 64,217
- In genetics: 2,786
- Year to date:
- Site-wide: 149,714
- Since beginning of last month:
- Site-wide: 142,829
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!