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

被引：582

作者：

Zheng, Jie ^{[1
]}

Erzurumluoglu, A. Mesut ^{[2
]}

Elsworth, Benjamin L. ^{[1
]}

Kemp, John P. ^{[3
]}

Howe, Laurence ^{[1
]}

Haycock, Philip C. ^{[1
]}

Hemani, Gibran ^{[1
]}

Tansey, Katherine ^{[1
]}

Laurin, Charles ^{[1
]}

St Pourcain, Beate ^{[1
]}

Warrington, Nicole M. ^{[3
]}

Finucane, Hilary K. ^{[4
]}

Price, Alkes L. ^{[4
,5
]}

Bulik-Sullivan, Brendan K. ^{[5
,6
,7
]}

Anttila, Verneri ^{[5
]}

Paternoster, Lavinia ^{[1
]}

Gaunt, Tom R. ^{[1
]}

Evans, David M. ^{[1
,3
]}

Neale, Benjamin M. ^{[5
,6
,7
]}

机构：

[1] Univ Bristol, MRC, Integrat Epidemiol Unit, Oakfield House, Bristol, Avon, England

[2] Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester, Leics, England

[3] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia

[4] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[5] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA

[6] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[7] Harvard Med Sch, Boston, MA USA

来源：

BIOINFORMATICS | 2017年 / 33卷 / 02期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; PARTITIONING HERITABILITY; SUSCEPTIBILITY LOCI; PROVIDES INSIGHTS; COMMON VARIANTS; IDENTIFIES; 11; METAANALYSIS; RISK; DISEASES; GLUCOSE;

D O I：

10.1093/bioinformatics/btw613

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：272 / 279

页数：8

共 61 条

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Monteleone, P. ;

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Valcarcel, Beatriz ;

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← 1 2 3 4 5 6 7 →

共 61 条

[1] Hundreds of variants clustered in genomic loci and biological pathways affect human height [J].

Allen, Hana Lango ;

Estrada, Karol ;

Lettre, Guillaume ;

Berndt, Sonja I. ;

Weedon, Michael N. ;

Rivadeneira, Fernando ;

Willer, Cristen J. ;

Jackson, Anne U. ;

Vedantam, Sailaja ;

Raychaudhuri, Soumya ;

Ferreira, Teresa ;

Wood, Andrew R. ;

Weyant, Robert J. ;

Segre, Ayellet V. ;

Speliotes, Elizabeth K. ;

Wheeler, Eleanor ;

Soranzo, Nicole ;

Park, Ju-Hyun ;

Yang, Jian ;

Gudbjartsson, Daniel ;

Heard-Costa, Nancy L. ;

Randall, Joshua C. ;

Qi, Lu ;

Smith, Albert Vernon ;

Maegi, Reedik ;

Pastinen, Tomi ;

Liang, Liming ;

Heid, Iris M. ;

Luan, Jian'an ;

Thorleifsson, Gudmar ;

Winkler, Thomas W. ;

Goddard, Michael E. ;

Lo, Ken Sin ;

Palmer, Cameron ;

Workalemahu, Tsegaselassie ;

Aulchenko, Yurii S. ;

Johansson, Asa ;

Zillikens, M. Carola ;

Feitosa, Mary F. ;

Esko, Tonu ;

Johnson, Toby ;

Ketkar, Shamika ;

Kraft, Peter ;

Mangino, Massimo ;

Prokopenko, Inga ;

Absher, Devin ;

Albrecht, Eva ;

Ernst, Florian ;

Glazer, Nicole L. ;

Hayward, Caroline .

NATURE, 2010, 467 (7317) :832-838

[2] An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[3] Integrating common and rare genetic variation in diverse human populations [J].

Altshuler, David M. ;

Gibbs, Richard A. ;

Peltonen, Leena ;

Dermitzakis, Emmanouil ;

Schaffner, Stephen F. ;

Yu, Fuli ;

Bonnen, Penelope E. ;

de Bakker, Paul I. W. ;

Deloukas, Panos ;

Gabriel, Stacey B. ;

Gwilliam, Rhian ;

Hunt, Sarah ;

Inouye, Michael ;

Jia, Xiaoming ;

Palotie, Aarno ;

Parkin, Melissa ;

Whittaker, Pamela ;

Chang, Kyle ;

Hawes, Alicia ;

Lewis, Lora R. ;

Ren, Yanru ;

Wheeler, David ;

Muzny, Donna Marie ;

Barnes, Chris ;

Darvishi, Katayoon ;

Hurles, Matthew ;

Korn, Joshua M. ;

Kristiansson, Kati ;

Lee, Charles ;

McCarroll, Steven A. ;

Nemesh, James ;

Keinan, Alon ;

Montgomery, Stephen B. ;

Pollack, Samuela ;

Price, Alkes L. ;

Soranzo, Nicole ;

Gonzaga-Jauregui, Claudia ;

Anttila, Verneri ;

Brodeur, Wendy ;

Daly, Mark J. ;

Leslie, Stephen ;

McVean, Gil ;

Moutsianas, Loukas ;

Nguyen, Huy ;

Zhang, Qingrun ;

Ghori, Mohammed J. R. ;

McGinnis, Ralph ;

McLaren, William ;

Takeuchi, Fumihiko ;

Grossman, Sharon R. .

NATURE, 2010, 467 (7311) :52-58

[4]

[Anonymous], 2010, PLOS GENET, V6

[5] The use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data [J].

Bataille, V. ;

Lens, M. ;

Spector, T. D. .

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2012, 26 (09) :1067-1073

[6] Childhood intelligence is heritable, highly polygenic and associated with FNBP1L [J].

Benyamin, B. ;

St Pourcain, B. ;

Davis, O. S. ;

Davies, G. ;

Hansell, N. K. ;

Brion, M-J A. ;

Kirkpatrick, R. M. ;

Cents, R. A. M. ;

Franic, S. ;

Miller, M. B. ;

Haworth, C. M. A. ;

Meaburn, E. ;

Price, T. S. ;

Evans, D. M. ;

Timpson, N. ;

Kemp, J. ;

Ring, S. ;

McArdle, W. ;

Medland, S. E. ;

Yang, J. ;

Harris, S. E. ;

Liewald, D. C. ;

Scheet, P. ;

Xiao, X. ;

Hudziak, J. J. ;

de Geus, E. J. C. ;

Jaddoe, V. W. V. ;

Starr, J. M. ;

Verhulst, F. C. ;

Pennell, C. ;

Tiemeier, H. ;

Iacono, W. G. ;

Palmer, L. J. ;

Montgomery, G. W. ;

Martin, N. G. ;

Boomsma, D. I. ;

Posthuma, D. ;

McGue, M. ;

Wright, M. J. ;

Smith, G. Davey ;

Deary, I. J. ;

Plomin, R. ;

Visscher, P. M. .

MOLECULAR PSYCHIATRY, 2014, 19 (02) :253-258

[7] Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture [J].

Berndt, Sonja I. ;

Gustafsson, Stefan ;

Maegi, Reedik ;

Ganna, Andrea ;

Wheeler, Eleanor ;

Feitosa, Mary F. ;

Justice, Anne E. ;

Monda, Keri L. ;

Croteau-Chonka, Damien C. ;

Day, Felix R. ;

Esko, Tonu ;

Fall, Tove ;

Ferreira, Teresa ;

Gentilini, Davide ;

Jackson, Anne U. ;

Luan, Jian'an ;

Randall, Joshua C. ;

Vedantam, Sailaja ;

Willer, Cristen J. ;

Winkler, Thomas W. ;

Wood, Andrew R. ;

Workalemahu, Tsegaselassie ;

Hu, Yi-Juan ;

Lee, Sang Hong ;

Liang, Liming ;

Lin, Dan-Yu ;

Min, Josine L. ;

Neale, Benjamin M. ;

Thorleifsson, Gudmar ;

Yang, Jian ;

Albrecht, Eva ;

Amin, Najaf ;

Bragg-Gresham, Jennifer L. ;

Cadby, Gemma ;

den Heijer, Martin ;

Eklund, Niina ;

Fischer, Krista ;

Goel, Anuj ;

Hottenga, Jouke-Jan ;

Huffman, Jennifer E. ;

Jarick, Ivonne ;

Johansson, Asa ;

Johnson, Toby ;

Kanoni, Stavroula ;

Kleber, Marcus E. ;

Koenig, Inke R. ;

Kristiansson, Kati ;

Kutalik, Zoltn ;

Lamina, Claudia ;

Lecoeur, Cecile .

NATURE GENETICS, 2013, 45 (05) :501-U69

[8] A genome-wide association study of anorexia nervosa [J].

Boraska, V. ;

Franklin, C. S. ;

Floyd, J. A. B. ;

Thornton, L. M. ;

Huckins, L. M. ;

Southam, L. ;

Rayner, N. W. ;

Tachmazidou, I. ;

Klump, K. L. ;

Treasure, J. ;

Lewis, C. M. ;

Schmidt, U. ;

Tozzi, F. ;

Kiezebrink, K. ;

Hebebrand, J. ;

Gorwood, P. ;

Adan, R. A. H. ;

Kas, M. J. H. ;

Favaro, A. ;

Santonastaso, P. ;

Fernandez-Aranda, F. ;

Gratacos, M. ;

Rybakowski, F. ;

Dmitrzak-Weglarz, M. ;

Kaprio, J. ;

Keski-Rahkonen, A. ;

Raevuori, A. ;

Van Furth, E. F. ;

't Landt, M. C. T. Slof-Op ;

Hudson, J. I. ;

Reichborn-Kjennerud, T. ;

Knudsen, G. P. S. ;

Monteleone, P. ;

Kaplan, A. S. ;

Karwautz, A. ;

Hakonarson, H. ;

Berrettini, W. H. ;

Guo, Y. ;

Li, D. ;

Schork, N. J. ;

Komaki, G. ;

Ando, T. ;

Inoko, H. ;

Esko, T. ;

Fischer, K. ;

Maennik, K. ;

Metspalu, A. ;

Baker, J. H. ;

Cone, R. D. ;

Dackor, J. .

MOLECULAR PSYCHIATRY, 2014, 19 (10) :1085-1094

[9] A genome-wide association meta-analysis identifies new childhood obesity loci [J].

Bradfield, Jonathan P. ;

Taal, H. Rob ;

Timpson, Nicholas J. ;

Scherag, Andre ;

Lecoeur, Cecile ;

Warrington, Nicole M. ;

Hypponen, Elina ;

Holst, Claus ;

Valcarcel, Beatriz ;

Thiering, Elisabeth ;

Salem, Rany M. ;

Schumacher, Fredrick R. ;

Cousminer, Diana L. ;

Sleiman, Patrick M. A. ;

Zhao, Jianhua ;

Berkowitz, Robert I. ;

Vimaleswaran, Karani S. ;

Jarick, Ivonne ;

Pennell, Craig E. ;

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