PhenoSpD: an integrated toolkit for phenotypic correlation estimation and multiple testing correction using GWAS summary statistics
Tom G Richardson,
Louise Amanda Claire Millard,
Tom R Gaunt
Posted 10 Jun 2017
bioRxiv DOI: 10.1101/148627 (published DOI: 10.1093/gigascience/giy090)
Posted 10 Jun 2017
Background: Identifying phenotypic correlations between complex traits and diseases can provide useful etiological insights. Restricted access to individual-level phenotype data makes it difficult to estimate large-scale phenotypic correlation across the human phenome. State-of-the-art methods, metaCCA and LD score regression, provide an alternative approach to estimate phenotypic correlation using genome-wide association study (GWAS) summary statistics. Results: Here, we present an integrated R toolkit, PhenoSpD, to 1) apply metaCCA (or LD score regression) to estimate phenotypic correlations using GWAS summary statistics; and 2) to utilize the estimated phenotypic correlations to inform correction of multiple testing for complex human traits using the spectral decomposition of matrices (SpD). The simulations suggest it is possible to estimate phenotypic correlation using samples with only a partial overlap, but as overlap decreases correlations will attenuate towards zero and multiple testing correction will be more stringent than in perfectly overlapping samples. In a case study, PhenoSpD using GWAS results suggested 324.4 independent tests among 452 metabolites, which is close to the 296 independent tests estimated using true phenotypic correlation. We further applied PhenoSpD to estimated 7,503 pair-wise phenotypic correlations among 123 metabolites using GWAS summary statistics from Kettunen et al. and PhenoSpD suggested 44.9 number of independent tests for theses metabolites. Conclusion: PhenoSpD integrates existing methods and provides a simple and conservative way to reduce dimensionality for complex human traits using GWAS summary statistics, which is particularly valuable for post-GWAS analysis of complex molecular traits. Availability: R code and documentation for PhenoSpD V1.0.0 is available online (https://github.com/MRCIEU/PhenoSpD).
- Downloaded 1,108 times
- Download rankings, all-time:
- Site-wide: 22,720
- In bioinformatics: 2,574
- Year to date:
- Site-wide: 95,332
- Since beginning of last month:
- Site-wide: 130,866
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!