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.
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.



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.



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.
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Jie
J
Zheng
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
A Mesut
AM
Erzurumluoglu
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Benjamin L
BL
Elsworth
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
John P
JP
Kemp
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Laurence
L
Howe
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Philip C
PC
Haycock
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Gibran
G
Hemani
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Katherine
K
Tansey
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Charles
C
Laurin
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Beate St
BS
Pourcain
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
Nicole M
NM
Warrington
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Hilary K
HK
Finucane
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alkes L
AL
Price
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Brendan K
BK
Bulik-Sullivan
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Verneri
V
Anttila
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Lavinia
L
Paternoster
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.
Tom R
TR
Gaunt
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol, UK.|University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
David M
DM
Evans
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Benjamin M
BM
Neale
D030561:Databases, Nucleic Acid; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018401:Sample Size; D012984:Software
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7
19474294
Nat Genet. 2010 Jul;42(7):565-9
20562875
Nature. 2012 Nov 1;491(7422):56-65
23128226
Genetics. 1916 Mar;1(2):164-76
17245854
Ann Hum Genet. 2013 Jan;77(1):67-79
23278391
Annu Rev Genomics Hum Genet. 2015;16:327-50
25939054
Nat Genet. 2015 Mar;47(3):291-5
25642630
Am J Hum Genet. 2014 Nov 6;95(5):535-52
25439723
Nucleic Acids Res. 2014 Jan;42(Database issue):D1001-6
24316577
Bioinformatics. 2012 Oct 1;28(19):2540-2
22843982
Am J Hum Genet. 2011 Mar 11;88(3):294-305
21376301
Nat Genet. 2015 Nov;47(11):1236-41
26414676
Nature. 2010 Sep 2;467(7311):52-8
20811451
Nat Genet. 2015 Nov;47(11):1228-35
26414678
Nat Genet. 2007 May;39(5):650-4
17417636
Am J Hum Genet. 2011 Jan 7;88(1):76-82
21167468
PLoS Genet. 2010 Aug 12;6(8):null
20714348
Am J Hum Genet. 2012 Dec 7;91(6):1011-21
23217325
J Eur Acad Dermatol Venereol. 2012 Sep;26(9):1067-73
22243446
Int J Epidemiol. 2003 Feb;32(1):1-22
12689998
Diabetes. 2016 Mar;65(3):803-17
26631737
Nat Genet. 2010 May;42(5):441-7
20418890
Diabetes. 2010 Dec;59(12):3229-39
20858683
Nat Genet. 2011 Sep 18;43(10):977-83
21926972
Nat Genet. 2012 Apr 15;44(5):532-538
22504419
PLoS One. 2015 Mar 26;10(3):e0119752
25811787
Hum Mol Genet. 2015 Feb 15;24(4):1155-68
25281659
Nat Commun. 2016 Mar 23;7:11122
27005778
Nature. 2014 Jul 24;511(7510):421-7
25056061
Nat Genet. 2009 Dec;41(12):1308-12
19915575
Nat Genet. 2015 Sep;47(9):979-986
26192919
Mol Psychiatry. 2014 Feb;19(2):253-8
23358156
Nature. 2007 Jul 26;448(7152):470-3
17611496
Nature. 2014 Oct 02;514(7520):92-97
25231870
Behav Genet. 2014 Jul;44(4):295-313
24828478
Nature. 2010 Oct 14;467(7317):832-8
20881960
Nature. 2010 Aug 5;466(7307):707-13
20686565
Nat Commun. 2016 Jan 21;7:10023
26831199
Nat Genet. 2010 Nov;42(11):937-48
20935630
Nature. 2014 Feb 20;506(7488):376-81
24390342
Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13790-4
25201988
Mol Psychiatry. 2012 Mar;17(3):337-49
21173776
Nat Genet. 2012 Apr 15;44(5):491-501
22504420
Nat Genet. 2013 May;45(5):501-12
23563607
Mol Psychiatry. 2013 Apr;18(4):497-511
22472876
Nat Genet. 2012 May;44(5):526-31
22484627
Nat Genet. 2012 May 13;44(6):659-69
22581228
Nat Genet. 2013 Dec;45(12):1452-8
24162737
Science. 2013 Jun 21;340(6139):1467-71
23722424
Nat Genet. 2015 Dec;47(12):1449-1456
26482879
J Am Acad Child Adolesc Psychiatry. 2010 Sep;49(9):884-97
20732625
Nat Genet. 2015 Oct;47(10):1121-1130
26343387
Nat Genet. 2013 Jan;45(1):76-82
23202124
Nature. 2015 Feb 12;518(7538):187-196
25673412
PLoS Genet. 2012;8(3):e1002607
22479202
Mol Psychiatry. 2014 Oct;19(10):1085-94
24514567
Nat Genet. 2012 Sep;44(9):981-90
22885922
Nat Genet. 2010 Feb;42(2):142-8
20081857
Lancet. 2013 Apr 20;381(9875):1371-1379
23453885
Nat Genet. 2010 Feb;42(2):105-16
20081858