Components of genetic associations across 2,138 phenotypes in the UK Biobank highlight novel adipocyte biology
Johanne M. Justesen,
Chong Yon Park,
Manuel A Rivas
Posted 14 Oct 2018
bioRxiv DOI: 10.1101/442715 (published DOI: 10.1038/s41467-019-11953-9)
Posted 14 Oct 2018
Population-based biobanks with genomic and dense phenotype data provide opportunities for generating effective therapeutic hypotheses and understanding the genomic role in disease predisposition. To characterize latent components of genetic associations, we applied truncated singular value decomposition (DeGAs) to matrices of summary statistics derived from genome-wide association analyses across 2,138 phenotypes measured in 337,199 White British individuals in the UK Biobank study. We systematically identified key components of genetic associations and the contributions of variants, genes, and phenotypes to each component. As an illustration of the utility of the approach to inform downstream experiments, we report putative loss of function variants, rs114285050 (GPR151) and rs150090666 (PDE3B), that substantially contribute to obesity-related traits, and experimentally demonstrate the role of these genes in adipocyte biology. Our approach to dissect components of genetic associations across the human phenome will accelerate biomedical hypothesis generation by providing insights on previously unexplored latent structures.
- Downloaded 1,543 times
- Download rankings, all-time:
- Site-wide: 5,995 out of 94,912
- In genetics: 440 out of 4,824
- Year to date:
- Site-wide: 22,310 out of 94,912
- Since beginning of last month:
- Site-wide: 45,243 out of 94,912
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!