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

GigaScience
Jie ZhengTom R Gaunt

Abstract

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 multi...Continue Reading

References

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Citations

Apr 30, 2019·Royal Society Open Science·Rebecca B LawnMarcus R Munafò
May 12, 2020·PLoS Genetics·Beate LeppertEvie Stergiakouli
May 15, 2020·International Journal of Molecular Sciences·Yury A BarbitoffAndrey S Glotov
Jul 19, 2019·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Ryan J LangdonPhilip Haycock
Mar 12, 2021·The Journal of Clinical Endocrinology and Metabolism·Maxime TremblayBenoit J Arsenault
Jun 27, 2021·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Gabriela A Martinez-LevyCarlos S Cruz-Fuentes
Dec 17, 2021·Frontiers in Cell and Developmental Biology·Sen LiTingting Yu

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Software Mentioned

R
metaCCA
SNPSpD
Base
GIANT
MAGIC
PheWAS
MR
PhenoSpD

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