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LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis

Jie Zheng, A. Mesut Erzurumluoglu, Benjamin L. Elsworth, Laurence Howe, Philip C. Haycock, Gibran Hemani, Katherine Tansey, Charles Laurin, Early Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium, Beate St. Pourcain, Nicole M. Warrington, Hilary K. Finucane, Alkes L. Price, Brendan K. Bulik-Sullivan, Verneri Anttila, Lavinia Paternoster, Tom R. Gaunt, David M. Evans, Benjamin M. Neale
doi: https://doi.org/10.1101/051094
Jie Zheng
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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  • For correspondence: jie.zheng@bristol.ac.uk
A. Mesut Erzurumluoglu
2Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK
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Benjamin L. Elsworth
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Laurence Howe
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Philip C. Haycock
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Gibran Hemani
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Katherine Tansey
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Charles Laurin
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Beate St. Pourcain
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Nicole M. Warrington
3University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia
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Hilary K. Finucane
4Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
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Alkes L. Price
4Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
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Brendan K. Bulik-Sullivan
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
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Verneri Anttila
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
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Lavinia Paternoster
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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Tom R. Gaunt
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
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David M. Evans
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK
3University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia
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Benjamin M. Neale
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
6Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Abstract

Motivation LD score regression is a reliable and efficient method of using genome-wide association study (GWAS) summary-level results data to estimate the SNP heritability of complex traits and diseases, partition this heritability into functional categories, and estimate the genetic correlation between different phenotypes. Because the method relies on summary level results data, LD score regression is computationally tractable even for very large sample sizes. However, publicly available GWAS summary-level data are typically stored in different databases and have different formats, making it difficult to apply LD score regression to estimate genetic correlations across many different traits simultaneously.

Results In this manuscript, we describe LD Hub – a centralized database of summary-level GWAS results for 177 diseases/traits from different publicly available resources/consortia and a web interface that automates the LD score regression analysis pipeline. To demonstrate functionality and validate our software, we replicated previously reported LD score regression analyses of 49 traits/diseases using LD Hub; and estimated SNP heritability and the genetic correlation across the different phenotypes. We also present new results obtained by uploading a recent atopic dermatitis GWAS meta-analysis to examine the genetic correlation between the condition and other potentially related traits. In response to the growing availability of publicly accessible GWAS summary-level results data, our database and the accompanying web interface will ensure maximal uptake of the LD score regression methodology, provide a useful database for the public dissemination of GWAS results, and provide a method for easily screening hundreds of traits for overlapping genetic aetiologies.

Availability and implementation The web interface and instructions for using LD Hub are available at http://ldsc.broadinstitute.org/

Footnotes

  • ↵† Joint senior authors

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LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis
Jie Zheng, A. Mesut Erzurumluoglu, Benjamin L. Elsworth, Laurence Howe, Philip C. Haycock, Gibran Hemani, Katherine Tansey, Charles Laurin, Early Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium, Beate St. Pourcain, Nicole M. Warrington, Hilary K. Finucane, Alkes L. Price, Brendan K. Bulik-Sullivan, Verneri Anttila, Lavinia Paternoster, Tom R. Gaunt, David M. Evans, Benjamin M. Neale
bioRxiv 051094; doi: https://doi.org/10.1101/051094
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LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis
Jie Zheng, A. Mesut Erzurumluoglu, Benjamin L. Elsworth, Laurence Howe, Philip C. Haycock, Gibran Hemani, Katherine Tansey, Charles Laurin, Early Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium, Beate St. Pourcain, Nicole M. Warrington, Hilary K. Finucane, Alkes L. Price, Brendan K. Bulik-Sullivan, Verneri Anttila, Lavinia Paternoster, Tom R. Gaunt, David M. Evans, Benjamin M. Neale
bioRxiv 051094; doi: https://doi.org/10.1101/051094

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