Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights
Hilary K. Finucane,
Schizophrenia Working Group of the Psychiatric Genomics Consortium,
Michael C O’Donovan,
Gregory E. Crawford,
Patrick F Sullivan,
Alkes L. Price
Posted 02 Aug 2016
bioRxiv DOI: 10.1101/067355 (published DOI: 10.1038/s41588-018-0092-1)
Posted 02 Aug 2016
Genome-wide association studies (GWAS) have identified over 100 risk loci for schizophrenia, but the causal mechanisms remain largely unknown. We performed a transcriptome-wide association study (TWAS) integrating expression data from brain, blood, and adipose tissues across 3,693 individuals with schizophrenia GWAS of 79,845 individuals from the Psychiatric Genomics Consortium. We identified 157 genes with a transcriptome-wide significant association, of which 35 did not overlap a known GWAS locus; the largest number involved alternative splicing in brain. 42/157 genes were also associated to specific chromatin phenotypes measured in 121 independent samples (a 4-fold enrichment over background genes). This high-throughput connection of GWAS findings to specific genes, tissues, and regulatory mechanisms is an essential step toward understanding the biology of schizophrenia and moving towards therapeutic interventions.
- Downloaded 2,506 times
- Download rankings, all-time:
- Site-wide: 2,488 out of 88,628
- In genomics: 474 out of 5,654
- Year to date:
- Site-wide: 63,800 out of 88,628
- Since beginning of last month:
- Site-wide: 55,049 out of 88,628
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!