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Multicenter Study
. 2017 Jan 15;33(2):272-279.
doi: 10.1093/bioinformatics/btw613. Epub 2016 Sep 22.

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

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Free PMC article
Multicenter Study

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 et al. Bioinformatics. .
Free PMC article

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 173 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/ CONTACT: jie.zheng@bristol.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.

Figures

Fig. 1.
Fig. 1.
Scope and features of LD Hub. The LD Hub server provides three features: (i) Test Centre, which is an automatic LD score regression platform, (ii) Lookup Center, which allows users to lookup LD score regression results for their trait(s) of interest and (iii) GWAShare Center, which allows users to share their GWAS summary results and contribute to the field
Fig. 2.
Fig. 2.
Contents of LD Hub. In total, data for 173 traits are included in LD Hub, which consist of 18 diseases, 48 complex traits and 107 metabolites
Fig. 3.
Fig. 3.
Schematic of LD Hub workflow. To start using LD Hub, users are required to login using a GMail (compatible) account. Once logged in, the users can then navigate their way around, selecting the features and databases they are interested in
Fig 4
Fig 4
Comparison of genetic correlation results between LD Hub and previously reported LD score regression results. Double blue lines represent genetic correlation results from LD Hub, and the black single lines represent genetic correlation results from previously reported LD score regression results. The discrepancies can be attributed to the minor changes in the quality control processes and the replacement of some GWAS results with more recent versions

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References

    1. 1000 Genomes Project Consortium. (2012) An integrated map of genetic variation from 1,092 human genomes. Nature, 491, 56–65. [TQ1] - PMC - PubMed
    1. Bataille V. et al. (2012) The use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data. J. Eur. Acad. Dermatol. Venereol., 26, 1067–1073. - PubMed
    1. Benyamin B. et al. (2013) Childhood intelligence is heritable, highly polygenic and associated with FNBP1L. Mol. Psychiatry, 19, 253–258. - PMC - PubMed
    1. Berndt S. et al. (2013) Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nat. Genet., 45, 501–512. - PMC - PubMed
    1. Boraska V. et al. (2014) A genome-wide association study of anorexia nervosa. Mol. Psychiatry, 19, 1085–1094. - PMC - PubMed

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