CoChat
Sign Up
Cited by 548Genetic Associations and EpidemiologyGenomics and Chromatin DynamicsGenetic Mapping and Diversity in Plants and Animals

The DOI matches its Crossref record; 89 of the 89 references it cites were found in a registry or an index.

Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

Open access
Gusev, Alexander, Lee, S. Hong, Trynka, Gosia, Finucane, Hilary, Vilhjálmsson, Bjarni J., Xu, Han, Zang, Chongzhi, Ripke, Stephan, Bulik-Sullivan, Brendan, Stahl, Eli, Kähler, Anna K., Hultman, Christina M., Purcell, Shaun M., McCarroll, Steven A., Daly, Mark, Pasaniuc, Bogdan, Sullivan, Patrick F., Neale, Benjamin M., Wray, Naomi R., Raychaudhuri, Soumya, Price, Alkes L., Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Walters, James T.R., Farh, Kai-How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Børglum, Anders D., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberly D., Chan, Raymond C.K., Chen, Ronald Y.L., Chen, Eric Y.H., Cheng, Wei, Cheung, Eric F.C., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Davis, Kenneth L., Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E., Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Gershon, Elliot S., Giegling, Ina, Giusti-Rodrguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, Grove, Jakob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kelly, Brian J., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Keong, Jimmy Lee Chee, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lnnqvist, Jouko, Macek, Milan, Magnusson, Patrik K.E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Morris, Derek W., Mors, Ole, Mortensen, Preben B., Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Mller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O’Callaghan, Eadbhard, O’Dushlaine, Colm, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Van Os, Jim, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietilinen, Olli, Pimm, Jonathan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Spencer, Chris C.A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T. Scott, Subramaniam, Mythily, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Sderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tooney, Paul A., Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H.M., Wormley, Brandon K., Wu, Jing Qin, Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Andreassen, Ole A., Blackwood, Douglas H.R., Bramon, Elvira, Buxbaum, Joseph D., Brglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., McQuillin, Andrew, Moran, Jennifer L., Mortensen, Preben B., Mowry, Bryan J., Nthen, Markus M., Ophoff, Roel A., Owen, Michael J., Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Rietschel, Marcella, Riley, Brien P., Rujescu, Dan, Sham, Pak C., Sklar, Pamela, St. Clair, David, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Sullivan, Patrick F., O’Donovan, Michael C., Ripke, Stephan, O’Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L., Kähler, Anna K., Akterin, Susanne, Bergen, Sarah, Magnusson, Patrik K.E., Neale, Benjamin M., Ruderfer, Douglas, Scolnick, Edward, Purcell, Shaun, McCarroll, Steve, Sklar, Pamela, Hultman, Christina M., Sullivan, Patrick F.·2014·The American Journal of Human Genetics
DOI 10.1016/j.ajhg.2014.10.004PMC PMC4225595
Open this paper in CoChat — free accountOpen PDF

Abstract

Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment; p = 3.7 × 10(-17)) and 38% (SE = 4%) of hg(2) from genotyped SNPs (1.6× enrichment, p = 1.0 × 10(-4)). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of hg(2) despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.ajhg.2014.10.004

Cites

89 of 89 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 88 references

Cited by

Sorted by citations

Items 501–548 of 548

Related

See all

Metadata

Authors
Gusev, A., Lee, S. H., Trynka, G., Finucane, H., Vilhjálmsson, B. J., Xu, H., Zang, C., Ripke, S., Bulik-Sullivan, B., Stahl, E., Kähler, A. K., Hultman, C. M., Purcell, S. M., McCarroll, S. A., Daly, M., Pasaniuc, B., Sullivan, P. F., Neale, B. M., Wray, N. R., Raychaudhuri, S., Price, A. L., Ripke, S., Neale, B. M., Corvin, A., Walters, J. T. R., Farh, K.-H., Holmans, P. A., Lee, P., Bulik-Sullivan, B., Collier, D. A., Huang, H., Pers, T. H., Agartz, I., Agerbo, E., Albus, M., Alexander, M., Amin, F., Bacanu, S. A., Begemann, M., Belliveau, R. A., Bene, J., Bergen, S. E., Bevilacqua, E., Bigdeli, T. B., Black, D. W., Børglum, A. D., Bruggeman, R., Buccola, N. G., Buckner, R. L., Byerley, W., Cahn, W., Cai, G., Campion, D., Cantor, R. M., Carr, V. J., Carrera, N., Catts, S. V., Chambert, K. D., Chan, R. C. K., Chen, R. Y. L., Chen, E. Y. H., Cheng, W., Cheung, E. F. C., Chong, S. A., Cloninger, C. R., Cohen, D., Cohen, N., Cormican, P., Craddock, N., Crowley, J. J., Curtis, D., Davidson, M., Davis, K. L., Degenhardt, F., Del Favero, J., DeLisi, L. E., Demontis, D., Dikeos, D., Dinan, T., Djurovic, S., Donohoe, G., Drapeau, E., Duan, J., Dudbridge, F., Durmishi, N., Eichhammer, P., Eriksson, J., Escott-Price, V., Essioux, L., Fanous, A. H., Farrell, M. S., Frank, J., Franke, L., Freedman, R., Freimer, N. B., Friedl, M., Friedman, J. I., Fromer, M., Genovese, G., Georgieva, L., Gershon, E. S., Giegling, I., Giusti-Rodrguez, P., Godard, S., Goldstein, J. I., Golimbet, V., Gopal, S., Gratten, J., Grove, J., de Haan, L., Hammer, C., Hamshere, M. L., Hansen, M., Hansen, T., Haroutunian, V., Hartmann, A. M., Henskens, F. A., Herms, S., Hirschhorn, J. N., Hoffmann, P., Hofman, A., Hollegaard, M. V., Hougaard, D. M., Ikeda, M., Joa, I., Julià, A., Kahn, R. S., Kalaydjieva, L., Karachanak-Yankova, S., Karjalainen, J., Kavanagh, D., Keller, M. C., Kelly, B. J., Kennedy, J. L., Khrunin, A., Kim, Y., Klovins, J., Knowles, J. A., Konte, B., Kucinskas, V., Kucinskiene, Z. A., Kuzelova-Ptackova, H., Kähler, A. K., Laurent, C., Keong, J. L. C., Lee, S. H., Legge, S. E., Lerer, B., Li, M., Li, T., Liang, K.-Y., Lieberman, J., Limborska, S., Loughland, C. M., Lubinski, J., Lnnqvist, J., Macek, M., Magnusson, P. K. E., Maher, B. S., Maier, W., Mallet, J., Marsal, S., Mattheisen, M., Mattingsdal, M., McCarley, R. W., McDonald, C., McIntosh, A. M., Meier, S., Meijer, C. J., Melegh, B., Melle, I., Mesholam-Gately, R. I., Metspalu, A., Michie, P. T., Milani, L., Milanova, V., Mokrab, Y., Morris, D. W., Mors, O., Mortensen, P. B., Murphy, K. C., Murray, R. M., Myin-Germeys, I., Mller-Myhsok, B., Nelis, M., Nenadic, I., Nertney, D. A., Nestadt, G., Nicodemus, K. K., Nikitina-Zake, L., Nisenbaum, L., Nordin, A., O’Callaghan, E., O’Dushlaine, C., O’Neill, F. A., Oh, S.-Y., Olincy, A., Olsen, L., Van Os, J., Pantelis, C., Papadimitriou, G. N., Papiol, S., Parkhomenko, E., Pato, M. T., Paunio, T., Pejovic-Milovancevic, M., Perkins, D. O., Pietilinen, O., Pimm, J., Pocklington, A. J., Powell, J., Price, A., Pulver, A. E., Purcell, S. M., Quested, D., Rasmussen, H. B., Reichenberg, A., Reimers, M. A., Richards, A. L., Roffman, J. L., Roussos, P., Ruderfer, D. M., Salomaa, V., Sanders, A. R., Schall, U., Schubert, C. R., Schulze, T. G., Schwab, S. G., Scolnick, E. M., Scott, R. J., Seidman, L. J., Shi, J., Sigurdsson, E., Silagadze, T., Silverman, J. M., Sim, K., Slominsky, P., Smoller, J. W., So, H.-C., Spencer, C. C. A., Stahl, E. A., Stefansson, H., Steinberg, S., Stogmann, E., Straub, R. E., Strengman, E., Strohmaier, J., Stroup, T. S., Subramaniam, M., Suvisaari, J., Svrakic, D. M., Szatkiewicz, J. P., Sderman, E., Thirumalai, S., Toncheva, D., Tooney, P. A., Tosato, S., Veijola, J., Waddington, J., Walsh, D., Wang, D., Wang, Q., Webb, B. T., Weiser, M., Wildenauer, D. B., Williams, N. M., Williams, S., Witt, S. H., Wolen, A. R., Wong, E. H. M., Wormley, B. K., Wu, J. Q., Xi, H. S., Zai, C. C., Zheng, X., Zimprich, F., Wray, N. R., Stefansson, K., Visscher, P. M., Adolfsson, R., Andreassen, O. A., Blackwood, D. H. R., Bramon, E., Buxbaum, J. D., Brglum, A. D., Cichon, S., Darvasi, A., Domenici, E., Ehrenreich, H., Esko, T., Gejman, P. V., Gill, M., Gurling, H., Hultman, C. M., Iwata, N., Jablensky, A. V., Jönsson, E. G., Kendler, K. S., Kirov, G., Knight, J., Lencz, T., Levinson, D. F., Li, Q. S., Liu, J., Malhotra, A. K., McCarroll, S. A., McQuillin, A., Moran, J. L., Mortensen, P. B., Mowry, B. J., Nthen, M. M., Ophoff, R. A., Owen, M. J., Palotie, A., Pato, C. N., Petryshen, T. L., Posthuma, D., Rietschel, M., Riley, B. P., Rujescu, D., Sham, P. C., Sklar, P., St. Clair, D., Weinberger, D. R., Wendland, J. R., Werge, T., Daly, M. J., Sullivan, P. F., O’Donovan, M. C., Ripke, S., O’Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S., Magnusson, P. K. E., Neale, B. M., Ruderfer, D., Scolnick, E., Purcell, S., McCarroll, S., Sklar, P., Hultman, C. M., & Sullivan, P. F.
Affiliations
  • Harvard University (US)
  • Broad Institute (US)
  • Massachusetts Institute of Technology (US)
  • The University of Queensland (AU)
  • Karolinska Institutet (SE)
  • University of North Carolina at Chapel Hill (US)
  • University of California, Los Angeles (US)
Corresponding author
Gusev, Alexander
ORCID
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2014-11
Volume
95
Issue
5
Pages
535-552
ISSN
0002-9297 (ISSN-L)
DOI
10.1016/j.ajhg.2014.10.004
PMC
PMC4225595
OpenAlex
W2159417227
Cited by
544
References
88
Citations by year
2026: 16 · 2025: 26 · 2024: 30 · 2023: 29 · 2022: 56 · 2021: 42 · 2020: 43 · 2019: 58 · 2018: 59 · 2017: 65 · 2016: 73 · 2015: 45 · 2014: 2
FWCI
40.40
Type
journal article
Language
en
Open access
Licence
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • EPubDev Repository (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
  • Lirias (submittedVersion)
  • GRO (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion)
  • RUNE (Research UNE) (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • NOVA (University of Newcastle Australia) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • UNC Libraries
Funders
  • Hertz Foundation
  • Wellcome Trust (076113)
  • Lundbeckfonden (R155-2014-1724)
  • National Institutes of Health (5r01ar063759-07, 5u01mh094432-04)
  • Medical Research Council (MR/L010305/1)
  • Australian Research Council (FT0991360, DE130100614)
  • National Health and Medical Research Council (613602)
  • National Institute of Mental Health (U01MH096296, U01 MH094432, R01MH085548, T32MH020030, R01MH101244)
  • National Human Genome Research Institute (R03HG006731, 1U01HG0070033)
  • National Institute of General Medical Sciences (R01GM105857, F32GM106584)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR063759)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
regulatory variants, enhancers, common complex diseases, variance components, linkage disequilibrium, coding variants, rare coding variants, schizophrenia, genome-wide association study
MeSH terms
Computer Simulation, Humans, Models, Genetic, Genetic Variation, Open Reading Frames, Genetic Diseases, Inborn, Inheritance Patterns, Regulatory Elements, Transcriptional, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review