Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation
Olav B Smeland,
Alexey A. Shadrin,
Chun Chieh Fan,
Kevin S. O’Connell,
Wesley K. Thompson,
Ole A. Andreassen,
Anders M. Dale
Posted 27 Dec 2017
bioRxiv DOI: 10.1101/240275 (published DOI: 10.1038/s41467-019-10310-0)
Posted 27 Dec 2017
Accumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. While current cross-trait analytical methods focus on genetic correlation between traits, we developed a novel statistical tool (MiXeR), which quantifies polygenic overlap independent of genetic correlation, using summary statistics from GWAS. MiXeR results can be presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that more than 9K variants causally influence schizophrenia, 7K influence bipolar disorder, and out of those variants 6.9K are shared between these two disorders, which have high genetic correlation. Further, MiXeR uncovers extensive polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, these traits share more than 9K causal variants, while 3K additional variants only influence educational attainment. By considering the polygenicity, heritability and discoverability of complex phenotypes, MiXeR provides a more complete quantification of shared genetic architecture than offered by other available tools.
- Downloaded 1,173 times
- Download rankings, all-time:
- Site-wide: 9,157 out of 92,068
- In genetics: 643 out of 4,731
- Year to date:
- Site-wide: 47,214 out of 92,068
- Since beginning of last month:
- Site-wide: 29,357 out of 92,068
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!