Bipolar disorder (BD) affects the quality of life of approximately 1% of the population and represents a major public health concern. It is known to be highly heritable but large-scale genome-wide association studies (GWAS) have discovered only a handful of markers associated with the disease. Furthermore, the biological mechanisms underlying these markers need to be elucidated. We recently published a gene-level association test, PrediXcan that integrates transcriptome regulation data to characterize the function of these markers in a tissue specific manner. In this study, we developed prediction models for mRNA levels in 10 brain regions using data from the GTEx project and performed PrediXcan analysis in WTCCC as well as in an independent cohort, GAIN. We replicate the association between predicted expression of PTPRE and BD risk in whole blood and recapitulate the association in brain tissues. PTPRE encodes the protein tyrosine phosphatase, receptor type E, that is known to be involved in RAS signaling and activation of voltage-gated K+ channels. We also found a new genome-wide significant association between lower predicted expression of BBX (bobby sox homolog) in the anterior cingulate cortex region of the brain and increased risk of BD (pWTCCC = 7.02 x 10e-6, pGAIN = 4.68 x 10e-3, pmeta = 1.11 x 10e-7). In sum, we used our mechanistically informed approach, PrediXcan, to identify and replicate two novel genome-wide significant genes using existing GWAS studies.
- Downloaded 876 times
- Download rankings, all-time:
- Site-wide: 14,024 out of 88,858
- In genetics: 920 out of 4,603
- Year to date:
- Site-wide: 75,067 out of 88,858
- Since beginning of last month:
- Site-wide: 84,497 out of 88,858
Downloads over time
Distribution of downloads per paper, site-wide
- 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!