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Gigascience. 2018 Aug 1;7(8). doi: 10.1093/gigascience/giy090.

PhenoSpD: an integrated toolkit for phenotypic correlation estimation and multiple testing correction using GWAS summary statistics.

Author information

MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, BS8 2BN, UK.
Intelligent Systems Laboratory, University of Bristol, Tyndall Ave, Bristol, BS8 1TH, UK.
Åarhus Center for Bioinformatics BIRC, Aarhus University, Nordre Ringgade, 1,8000, Aarhus C, Denmark.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA.
Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.



Identifying phenotypic correlations between complex traits and diseases can provide useful etiological insights. Restricted access to much individual-level phenotype data makes it difficult to estimate large-scale phenotypic correlation across the human phenome. Two state-of-the-art methods, metaCCA and LD score regression, provide an alternative approach to estimate phenotypic correlation using only genome-wide association study (GWAS) summary results.


Here, we present an integrated R toolkit, PhenoSpD, to use LD score regression to estimate phenotypic correlations using GWAS summary statistics and 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 that it is possible to identify nonindependence of phenotypes using samples with partial overlap; as overlap decreases, the estimated phenotypic correlations will attenuate toward zero and multiple testing correction will be more stringent than in perfectly overlapping samples. Also, in contrast to LD score regression, metaCCA will provide approximate genetic correlations rather than phenotypic correlation, which limits its application for multiple testing correction. In a case study, PhenoSpD using UK Biobank GWAS results suggested 399.6 independent tests among 487 human traits, which is close to the 352.4 independent tests estimated using true phenotypic correlation. We further applied PhenoSpD to an estimated 5,618 pair-wise phenotypic correlations among 107 metabolites using GWAS summary statistics from Kettunen's publication and PhenoSpD suggested the equivalent of 33.5 independent tests for these metabolites.


PhenoSpD extends the use of summary-level results, providing a simple and conservative way to reduce dimensionality for complex human traits using GWAS summary statistics. This is particularly valuable in the age of large-scale biobank and consortia studies, where GWAS results are much more accessible than individual-level data.

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