The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease
Open accessAbstract
Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source says what the claim attributes to it.
In the citing paper
“Examples include the role of complement in the pathogenesis of acute macular degeneration38, synaptic pruning in schizophrenia64 and autophagy in inflammatory bowel disease65.”
From A brief history of human disease genetics (2020) · cites this paper as [65]
The cited source says what the claim attributes to it.
In the citing paper
“Population-based, genome-wide–association studies followed by subsequent meta-analysis of population-based, genome-wide–association studies and immunochip data have identified more than 160 loci linked to IBD susceptibility (Jostins et al., 2012).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Jostins et al., 2012
In the citing paper
“The 71 regulators significantly overlap with genes genetically associated with inflammatory bowel disease44 (11 of 71, p<10-9).”
From Dynamic regulatory network controlling TH17 cell differentiation (2013) · cites this paper as [44]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A General Framework for Weighted Gene Co-Expression Network Analysis
Zhang, B., & Horvath, S. (2005) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1128 · Cited by 5,684
Self-citationMolodecky, N. A., Soon, I. S., Rabi, D. M., Ghali, W. A., Ferris, M., Chernoff, G., Benchimol, E. I., Panaccione, R., Ghosh, S., Barkema, H. W., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.10.001 · Cited by 4,833
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013
Genetics and pathogenesis of inflammatory bowel disease
Khor, B., Gardet, A., & Xavier, R. J. (2011) · Nature · doi:10.1038/nature10209 · Cited by 2,733
Self-citationFranke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., et al. (2010) · Nature Genetics · doi:10.1038/ng.717 · Cited by 2,520
Self-citationThe mystery of missing heritability: Genetic interactions create phantom heritability
Zuk, O., Hechter, E., Sunyaev, S. R., & Lander, E. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119675109 · Cited by 1,542
Anderson, C. A., Boucher, G., Lees, C. W., Franke, A., D’Amato, M., Taylor, K. D., Lee, J. C., Goyette, P., Imielinski, M. B., Latiano, A., et al. (2011) · Nature Genetics · doi:10.1038/ng.764 · Cited by 1,334
Self-citationGenetics of gene expression and its effect on disease
Emilsson, V., Thorleifsson, G., Zhang, B., Leonardson, A. S., Zink, F., Zhu, J., Carlson, S., Helgason, A., Walters, G. B., Gunnarsdottir, S., et al. (2008) · Nature · doi:10.1038/nature06758 · Cited by 1,296
Self-citationSTAT3 Mutations in the Hyper-IgE Syndrome
Holland, S. M., DeLeo, F. R., Elloumi, H. Z., Hsu, A. P., Uzel, G., Brodsky, N. N., Freeman, A. F., Demidowich, A. P., Davis, J., Turner, M. L. C., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa073687 · Cited by 1,233
Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome
Minegishi, Y., Saitō, M., Tsuchiya, S., Tsuge, I., Takada, H., Hara, T., Kawamura, N., Ariga, T., Pašić, S., Stojković, O., et al. (2007) · Nature · doi:10.1038/nature06096 · Cited by 1,075
Cited by
Sorted by citations
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577
Self-citationIntegrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368
Self-citationLD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bulik-Sullivan, B. K., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., Daly, M. J., Price, A. L., & Neale, B. M. (2015) · Nature Genetics · doi:10.1038/ng.3211 · Cited by 5,559
Self-citationThe Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
The GTEx Consortium, Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., Tukiainen, T., et al. (2015) · Science · doi:10.1126/science.1262110 · Cited by 5,062
Self-citationAn atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255
Ungaro, R. C., Mehandru, S., Allen, P. B., Peyrin‐Biroulet, L., & Colombel, J. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32126-2 · Cited by 3,659
The Treatment-Naive Microbiome in New-Onset Crohn’s Disease
Gevers, D., Kugathasan, S., Denson, L. A., Vázquez-Baeza, Y., Van Treuren, W., Ren, B., Schwager, E., Knights, D., Song, S. J., Yassour, M., et al. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.005 · Cited by 3,220
Self-citationMulti-omics of the gut microbial ecosystem in inflammatory bowel diseases
Lloyd-Price, J., Arze, C., Ananthakrishnan, A. N., Schirmer, M., Avila-Pacheco, J., Poon, T. W., Andrews, E., Ajami, N. J., Bonham, K. S., Brislawn, C. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1237-9 · Cited by 3,143
Self-citationAn Expanded View of Complex Traits: From Polygenic to Omnigenic
Boyle, E. A., Li, Y. I., & Pritchard, J. K. (2017) · Cell · doi:10.1016/j.cell.2017.05.038 · Cited by 2,851
Torres, J., Mehandru, S., Colombel, J., & Peyrin‐Biroulet, L. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31711-1 · Cited by 2,833
Cytokines in inflammatory bowel disease
Neurath, M. F. (2014) · Nature Reviews Immunology · doi:10.1038/nri3661 · Cited by 2,706
The global burden of IBD: from 2015 to 2025
Kaplan, G. G. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.150 · Cited by 2,639
Partitioning heritability by functional annotation using genome-wide association summary statistics
ReproGen Consortium, Finucane, H. K., Schizophrenia Working Group of the Psychiatric Genomics Consortium, The RACI Consortium, Bulik-Sullivan, B., Gusev, A., Trynka, G., Reshef, Y., Loh, P.-R., Anttila, V., et al. (2015) · Nature Genetics · doi:10.1038/ng.3404 · Cited by 2,604
Self-citationLiu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C., Jostins, L., Shah, T., et al. (2015) · Nature Genetics · doi:10.1038/ng.3359 · Cited by 2,603
Self-citationGenomic atlas of the human plasma proteome
Sun, B. B., Maranville, J. C., Peters, J. E., Stacey, D., Staley, J. R., Blackshaw, J., Burgess, S., Jiang, T., Paige, E., Surendran, P., et al. (2018) · Nature · doi:10.1038/s41586-018-0175-2 · Cited by 2,268
Self-citationGlycosylation in health and disease
Reily, C., Stewart, T. J., Renfrow, M. B., & Novak, J. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0129-4 · Cited by 2,075
Probiotics and prebiotics in intestinal health and disease: from biology to the clinic
Sanders, M. E., Merenstein, D. J., Reid, G., Gibson, G. R., & Rastall, R. A. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0173-3 · Cited by 2,059
Analysis of shared heritability in common disorders of the brain
The Brainstorm Consortium, Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G. J., Gormley, P., et al. (2018) · Science · doi:10.1126/science.aap8757 · Cited by 1,924
Self-citationAutophagy in infection, inflammation and immunity
Deretic, V., Saitoh, T., & Akira, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3532 · Cited by 1,919
Magro, F., Gionchetti, P., Eliakim, R., Ardizzone, S., Armuzzi, A., Barreiro-de Acosta, M., Burisch, J., Gecse, K. B., Hart, A. L., Hindryckx, P., et al. (2017) · Journal of Crohn's and Colitis · doi:10.1093/ecco-jcc/jjx008 · Cited by 1,910
Self-citationMachiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., Ballet, V., Claes, K., Van Immerseel, F., Verbeke, K., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-304833 · Cited by 1,904
Self-citationThe Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead
Kostic, A. D., Xavier, R. J., & Gevers, D. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.009 · Cited by 1,789
Self-citationRegional specialization within the intestinal immune system
Mowat, A. M., & Agace, W. W. (2014) · Nature reviews. Immunology · doi:10.1038/nri3738 · Cited by 1,882
A gene-based association method for mapping traits using reference transcriptome data
Gamazon, E. R., Wheeler, H. E., Shah, K. P., Mozaffari, S. V., Aquino-Michaels, K., Carroll, R. J., Eyler, A. E., Denny, J. C., Nicolae, D. L., Cox, N. J., et al. (2015) · Nature Genetics · doi:10.1038/ng.3367 · Cited by 1,790
Berre, C. L., Honap, S., & Peyrin‐Biroulet, L. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00966-2 · Cited by 1,754
Kobayashi, T., Siegmund, B., Berre, C. L., Wei, S. C., Ferrante, M., Shen, B., Bernstein, C. N., Danese, S., Peyrin‐Biroulet, L., & Hibi∥, T. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-0205-x · Cited by 1,777
Epidemiology and risk factors for IBD
Ananthakrishnan, A. N. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.34 · Cited by 1,741
Self-citationImmunopathogenesis of IBD: current state of the art
de Souza, H. S. P., & Fiocchi, C. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.186 · Cited by 1,551
Inflammatory bowel disease: Pathogenesis
Zhang, Y.-Z. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i1.91 · Cited by 1,595
Genome-wide patterns of selection in 230 ancient Eurasians
Mathieson, I., Lazaridis, I., Rohland, N., Mallick, S., Patterson, N., Roodenberg, S. A., Harney, E., Stewardson, K., Fernandes, D., Novak, M., et al. (2015) · Nature · doi:10.1038/nature16152 · Cited by 1,515
Lamas, B., Richard, M. L., Leducq, V., Pham, H.-P., Michel, M.-L., Da Costa, G., Bridonneau, C., Jegou, S., Hoffmann, T. W., Natividad, J. M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4102 · Cited by 1,482
Self-citationde Lange, K. M., Moutsianas, L., Lee, J. C., Lamb, C. A., Luo, Y., Kennedy, N. A., Jostins, L., Rice, D. L., Gutierrez-Achury, J., Ji, S.-G., et al. (2017) · Nature Genetics · doi:10.1038/ng.3760 · Cited by 1,445
Self-citationAnalysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
International Multiple Sclerosis Genetics Consortium (IMSGC) (2013) · Nature Genetics · doi:10.1038/ng.2770 · Cited by 1,386
Self-citationIntra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis
Smillie, C. S., Biton, M., Ordovás-Montañés, J., Sullivan, K. M., Burgin, G., Graham, D. B., Herbst, R. H., Rogel, N., Slyper, M., Waldman, J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.06.029 · Cited by 1,417
Self-citationHow informative is the mouse for human gut microbiota research?
Nguyen, T. L. A., Vieira-Silva, S., Liston, A., & Raes, J. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.017400 · Cited by 1,334
“…a subset of patients Cannot capture the whole genetic heterogeneity of human IBD owing to the inherent genetic differences between the two species Jurjus et al., 2004; Barnett and Fraser, 2011 Chemically induced IBD Mostly resemble pathology of colitis as seen in a subset of IBD patients…”
BackgroundThe intestinal barrier: a fundamental role in health and disease
Vancamelbeke, M., & Vermeire, S. (2017) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2017.1343143 · Cited by 1,388
Self-citationFungal microbiota dysbiosis in IBD
Sokol, H., Leducq, V., Aschard, H., Pham, H., Jégou, S., Landman, C., Cohen, D., Liguori, G., Bourrier, A., Nion–Larmurier, I., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310746 · Cited by 1,382
Pathophysiology of Inflammatory Bowel Diseases
Chang, J. T. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2002697 · Cited by 1,295
Complex genetic signatures in immune cells underlie autoimmunity and inform therapy
Orrù, V., Steri, M., Sidore, C., Marongiu, M., Serra, V., Olla, S., Sole, G., Lai, S., Dei, M., Mulas, A., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0684-4 · Cited by 1,246
Understanding and Preventing the Global Increase of Inflammatory Bowel Disease
Kaplan, G. G., & Ng, S. C. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.10.020 · Cited by 1,224
The microbiome in early life: Implications for health outcomes
Tamburini, S., Shen, N., Wu, H. C., & Clemente, J. C. (2016) · Nature Medicine · doi:10.1038/nm.4142 · Cited by 1,213
Dynamics of the human gut microbiome in inflammatory bowel disease
Halfvarson, J., Brislawn, C. J., Lamendella, R., Vázquez-Baeza, Y., Walters, W. A., Bramer, L. M., D'Amato, M., Bonfiglio, F., McDonald, D., Gonzalez, A., et al. (2017) · Nature Microbiology · doi:10.1038/nmicrobiol.2017.4 · Cited by 1,204
Self-citationThe microbiome, cancer, and cancer therapy
Helmink, B. A., Khan, M. A. W., Hermann, A., Gopalakrishnan, V., & Wargo, J. A. (2019) · Nature Medicine · doi:10.1038/s41591-019-0377-7 · Cited by 1,200
Detection and interpretation of shared genetic influences on 42 human traits
Pickrell, J. K., Berisa, T., Liu, J. Z., Ségurel, L., Tung, J. Y., & Hinds, D. A. (2016) · Nature Genetics · doi:10.1038/ng.3570 · Cited by 1,151
Biology and therapeutic potential of interleukin-10
Saraiva, M., Vieira, P., & O’Garra, A. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190418 · Cited by 1,157
Finucane, H. K., Reshef, Y. A., Anttila, V., Slowikowski, K., Gusev, A., Byrnes, A., Gazal, S., Loh, P.-R., Lareau, C., Shoresh, N., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0081-4 · Cited by 1,097
Self-citationPleiotropy in complex traits: challenges and strategies
Solovieff, N., Cotsapas, C., Lee, P. H., Purcell, S. M., & Smoller, J. W. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3461 · Cited by 1,085
IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation
Ouyang, W., & O’Garra, A. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.020 · Cited by 1,141
Roda, G., Ng, S. C., Kotze, P. G., ARGOLLO, M. C., Panaccione, R., Spinelli, A., Kaser, A., Peyrin‐Biroulet, L., & Danese, S. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-0156-2 · Cited by 1,111
Impacts of gut bacteria on human health and diseases
Zhang, Y.-J., Li, S., Gan, R.-Y., Zhou, T., Xu, D.-P., & Li, H.-B. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16047493 · Cited by 1,055
Genetic determinants of the gut microbiome in UK twins
Goodrich, J. K., Davenport, E. R., Beaumont, M., Jackson, M. A., Knight, R., Ober, C., Spector, T. D., Bell, J. T., Clark, A. G., & Ley, R. E. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.04.017 · Cited by 1,048
Mechanisms of Disease: Inflammatory Bowel Diseases
Ramos, G. P., & Papadakis, K. A. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2018.09.013 · Cited by 1,073
Advantages and pitfalls in the application of mixed-model association methods
Yang, J., Zaitlen, N. A., Goddard, M. E., Visscher, P. M., & Price, A. L. (2014) · Nature Genetics · doi:10.1038/ng.2876 · Cited by 981
Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD
Na, Y. R., Stakenborg, M., Seok, S. H., & Matteoli, G. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0172-4 · Cited by 900
Diet, metabolites, and “western-lifestyle” inflammatory diseases
Thorburn, A. N., Macia, L., & Mackay, C. R. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.014 · Cited by 879
Teng, M. W. L., Bowman, E. P., McElwee, J. J., Smyth, M. J., Casanova, J., Cooper, A. M., & Cua, D. J. (2015) · Nature Medicine · doi:10.1038/nm.3895 · Cited by 905
The genetic architecture of the human cerebral cortex
Grasby, K. L., Jahanshad, N., Painter, J. N., Colodro-Conde, L., Bralten, J., Hibar, D. P., Lind, P. A., Pizzagalli, F., Ching, C. R. K., McMahon, M. A. B., et al. (2020) · Science · doi:10.1126/science.aay6690 · Cited by 876
Self-citationPrimary sclerosing cholangitis – a comprehensive review
Karlsen, T. H., Folseraas, T., Thorburn, D., & Vesterhus, M. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.07.022 · Cited by 868
Self-citationA compendium of chromatin contact maps reveals spatially active regions in the human genome
Schmitt, A. D., Hu, M., Jung, I., Xu, Z., Qiu, Y., Tan, C. L., Li, Y., Lin, S., Lin, Y., Barr, C. L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.061 · Cited by 866
Martin, J. P. D., Chang, C., Boschetti, G., Ungaro, R. C., Giri, M., Grout, J. A., Gettler, K., Chuang, L.-S. F., Nayar, S., Greenstein, A. J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.08.008 · Cited by 890
Self-citationColonic epithelial cell diversity in health and inflammatory bowel disease
Parikh, K., Antanaviciute, A., Fawkner-Corbett, D., Jagielowicz, M., Aulicino, A., Lagerholm, B. C., Davis, S. A., Kinchen, J. W., Chen, H. H., Alham, N. K., et al. (2019) · Nature · doi:10.1038/s41586-019-0992-y · Cited by 878
The microbiome and inflammatory bowel disease
Glassner, K. L., Abraham, B. P., & Quigley, E. M. M. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.11.003 · Cited by 875
SLC Transporters as Therapeutic Targets: Emerging Opportunities
Lin, L., Yee, S. W., Kim, R. B., & Giacomini, K. M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4626 · Cited by 835
NOD1 and NOD2: Signaling, Host Defense, and Inflammatory Disease
Caruso, R., Warner, N., Inohara, N., & Núñez, G. (2014) · Immunity · doi:10.1016/j.immuni.2014.12.010 · Cited by 830
GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment
Rietveld, C. A., Medland, S. E., Derringer, J., Yang, J., Esko, T., Martin, N. W., Westra, H.-J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., et al. (2013) · Science · doi:10.1126/science.1235488 · Cited by 827
Self-citationLewis, J. D., Chen, E. Z., Baldassano, R. N., Otley, A. R., Griffiths, A. M., Lee, D., Bittinger, K., Bailey, A., Friedman, E. S., Hoffmann, C., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.09.008 · Cited by 823
The effect of host genetics on the gut microbiome
Bonder, M. J., Kurilshikov, A., Tigchelaar, E. F., Mujagic, Z., Imhann, F., Vila, A. V., Deelen, P., Vatanen, T., Schirmer, M., Smeekens, S. P., et al. (2016) · Nature Genetics · doi:10.1038/ng.3663 · Cited by 819
Self-citationOxford IBD Cohort Investigators, West, N. R., Hegazy, A. N., Owens, B. M. J., Bullers, S. J., Linggi, B. E., Buonocore, S. M., Coccia, M., Görtz, D., This, S., et al. (2017) · Nature Medicine · doi:10.1038/nm.4307 · Cited by 812
Manzoni, C., Kia, D. A., Vandrovcová, J., Hardy, J., Wood, N. W., Lewis, P. A., & Ferrari, R. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw114 · Cited by 859
The gut microbiota and inflammatory bowel disease
Matsuoka, K., & Kanai, T. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-014-0454-4 · Cited by 804
Inflammatory Bowel Disease in Children and Adolescents
Rosen, M. J., Dhawan, A., & Saeed, S. A. (2015) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2015.1982 · Cited by 794
Imhann, F., Vich Vila, A., Bonder, M. J., Fu, J., Gevers, D., Visschedijk, M. C., Spekhorst, L. M., Alberts, R., Franke, L., van Dullemen, H. M., et al. (2018) · Gut · doi:10.1136/gutjnl-2016-312135 · Cited by 788
Self-citationBiological interpretation of genome-wide association studies using predicted gene functions
Pers, T. H., Karjalainen, J. M., Chan, Y., Westra, H.-J., Wood, A. R., Yang, J., Lui, J. C., Vedantam, S., Gustafsson, S., Esko, T., et al. (2015) · Nature Communications · doi:10.1038/ncomms6890 · Cited by 787
Self-citationCleynen, I., Boucher, G., Jostins, L., Schumm, L. P., Zeißig, S., Ahmad, T., Andersen, V. C., Andrews, J. M., Annese, V., Brand, S., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00465-1 · Cited by 784
Self-citationKhan, I., Ullah, N., Zha, L., Bai, Y., Khan, A., Zhao, T., Che, T., & Zhang, C. (2019) · Pathogens · doi:10.3390/pathogens8030126 · Cited by 771
Pathway paradigms revealed from the genetics of inflammatory bowel disease
Graham, D. B., & Xavier, R. J. (2020) · Nature · doi:10.1038/s41586-020-2025-2 · Cited by 801
Self-citationInnate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression
Fairfax, B. P., Humburg, P., Makino, S., Naranbhai, V., Wong, D., Lau, E., Jostins, L., Plant, K., Andrews, R., McGee, C., et al. (2014) · Science · doi:10.1126/science.1246949 · Cited by 764
Self-citationThe International IBD Genetics Consortium (IIBDGC), Ellinghaus, D., International Genetics of Ankylosing Spondylitis Consortium (IGAS), International PSC Study Group (IPSCSG), Genetic Analysis of Psoriasis Consortium (GAPC), Psoriasis Association Genetics Extension (PAGE), Jostins, L., Spain, S. L., Cortes, A., Bethune, J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3528 · Cited by 751
Self-citationCytokine Networks in the Pathophysiology of Inflammatory Bowel Disease
Friedrich, M., Pohin, M., & Powrie, F. M. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.017 · Cited by 776
Study, T. L. C., Yang, J., Bakshi, A., Zhu, Z., Hemani, G., Vinkhuyzen, A. A. E., Lee, S. H., Robinson, M. R., Perry, J. R. B., Nolte, I. M., et al. (2015) · Nature Genetics · doi:10.1038/ng.3390 · Cited by 745
Paneth cells as a site of origin for intestinal inflammation
Adolph, T. E., Tomczak, M. F., Niederreiter, L., Ko, H.-J., Böck, J., Martinez-Naves, E., Glickman, J. N., Tschurtschenthaler, M., Hartwig, J., Hosomi, S., et al. (2013) · Nature · doi:10.1038/nature12599 · Cited by 732
Self-citationTian, T., Wang, Z., & Zhang, J. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/4535194 · Cited by 740
The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease
Uhlig, H. H., Schwerd, T., Koletzko, S., Shah, N., Kammermeier, J., Elkadri, A. A., Ouahed, J., Wilson, D. C., Travis, S. P. L., Turner, D., et al. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.07.023 · Cited by 716
Self-citationMcKay, J., Hung, R. J., Han, Y., Zong, X., Carreras‐Torres, R., Christiani, D. C., Caporaso, N. E., Johansson, M., Xiao, X., Li, Y., et al. (2017) · Nature Genetics · doi:10.1038/ng.3892 · Cited by 720
Validating therapeutic targets through human genetics
Plenge, R. M., Scolnick, E. M., & Altshuler, D. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4051 · Cited by 712
Roles of intestinal epithelial cells in the maintenance of gut homeostasis
Okumura, R., & Takeda, K. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.20 · Cited by 732
Targeting immune cell circuits and trafficking in inflammatory bowel disease
Neurath, M. F. (2019) · Nature Immunology · doi:10.1038/s41590-019-0415-0 · Cited by 723
Evidence-based clinical practice guidelines for inflammatory bowel disease
Matsuoka, K., Kobayashi, T., Ueno, F., Matsui, T., Hirai, F., Inoue, N., Kato, J., Kobayashi, K., Kobayashi, K., Koganei, K., et al. (2018) · Journal of Gastroenterology · doi:10.1007/s00535-018-1439-1 · Cited by 698
A brief history of human disease genetics
Claussnitzer, M., Cho, J. H., Collins, R., Cox, N. J., Dermitzakis, E. T., Hurles, M. E., Kathiresan, S., Kenny, E. E., Lindgren, C. M., MacArthur, D. G., et al. (2020) · Nature · doi:10.1038/s41586-019-1879-7 · Cited by 697
The mycobiota: interactions between commensal fungi and the host immune system
Underhill, D. M., & Iliev, I. D. (2014) · Nature reviews. Immunology · doi:10.1038/nri3684 · Cited by 721
Dynamic regulatory network controlling TH17 cell differentiation
Yosef, N., Shalek, A. K., Gaublomme, J. T., Jin, H., Lee, Y., Awasthi, A., Wu, C., Karwacz, K., Xiao, S., Jorgolli, M., et al. (2013) · Nature · doi:10.1038/nature11981 · Cited by 682
Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
Chen, L., Ge, B., Casale, F. P., Vasquez, L., Kwan, T., Garrido-Martín, D., Watt, S., Yan, Y., Kundu, K., Ecker, S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.026 · Cited by 679
Önengüt-Gümüşcü, S., Chen, W., Burren, O. S., Cooper, N. J., Quinlan, A. R., Mychaleckyj, J. C., Farber, E., Bonnie, J. K., Szpak, M., Schofield, E. C., et al. (2015) · Nature Genetics · doi:10.1038/ng.3245 · Cited by 694
Self-citationPitfalls of predicting complex traits from SNPs
Wray, N. R., Yang, J., Hayes, B. J., Price, A. L., Goddard, M. E., & Visscher, P. M. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3457 · Cited by 690
Genome-wide enhancer maps link risk variants to disease genes
Nasser, J., Bergman, D. T., Fulco, C. P., Guckelberger, P., Doughty, B. R., Patwardhan, T. A., Jones, T. R., Nguyen, T. H., Ulirsch, J. C., Lekschas, F., et al. (2021) · Nature · doi:10.1038/s41586-021-03446-x · Cited by 669
Self-citationNOD proteins: regulators of inflammation in health and disease
Philpott, D. J., Sorbara, M. T., Robertson, S. J., Croitoru, K., & Girardin, S. E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3565 · Cited by 668
NLRP3 Inflammasome and Inflammatory Bowel Disease
Yu, Z., & Zhang, H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00276 · Cited by 671
Research Review: Polygenic methods and their application to psychiatric traits
Wray, N. R., Lee, S., Mehta, D., Vinkhuyzen, A. A. E., Dudbridge, F., & Middeldorp, C. M. (2014) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12295 · Cited by 683
Epidemiology and Pathogenesis of Ulcerative Colitis
Du, L., & Ha, C. Y. (2020) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2020.07.005 · Cited by 680
Human symptoms–disease network
Zhou, X., Menche, J., Barabási, A.-Ĺ., & Sharma, A. (2014) · Nature Communications · doi:10.1038/ncomms5212 · Cited by 659
Metadata
- Authors
- The International IBD Genetics Consortium (IIBDGC), Jostins, L., Ripke, S., Weersma, R. K., Duerr, R. H., McGovern, D. P., Hui, K. Y., Lee, J. C., Philip Schumm, L., Sharma, Y., Anderson, C. A., Essers, J., Mitrovic, M., Ning, K., Cleynen, I., Theatre, E., Spain, S. L., Raychaudhuri, S., Goyette, P., Wei, Z., Abraham, C., Achkar, J.-P., Ahmad, T., Amininejad, L., Ananthakrishnan, A. N., Andersen, V., Andrews, J. M., Baidoo, L., Balschun, T., Bampton, P. A., Bitton, A., Boucher, G., Brand, S., Büning, C., Cohain, A., Cichon, S., D’Amato, M., De Jong, D., Devaney, K. L., Dubinsky, M., Edwards, C., Ellinghaus, D., Ferguson, L. R., Franchimont, D., Fransen, K., Gearry, R., Georges, M., Gieger, C., Glas, J., Haritunians, T., Hart, A., Hawkey, C., Hedl, M., Hu, X., Karlsen, T. H., Kupcinskas, L., Kugathasan, S., Latiano, A., Laukens, D., Lawrance, I. C., Lees, C. W., Louis, E., Mahy, G., Mansfield, J., Morgan, A. R., Mowat, C., Newman, W., Palmieri, O., Ponsioen, C. Y., Potocnik, U., Prescott, N. J., Regueiro, M., Rotter, J. I., Russell, R. K., Sanderson, J. D., Sans, M., Satsangi, J., Schreiber, S., Simms, L. A., Sventoraityte, J., Targan, S. R., Taylor, K. D., Tremelling, M., Verspaget, H. W., De Vos, M., Wijmenga, C., Wilson, D. C., Winkelmann, J., Xavier, R. J., Zeissig, S., Zhang, B., Zhang, C. K., Zhao, H., Silverberg, M. S., Annese, V., Hakonarson, H., Brant, S. R., Radford-Smith, G., Mathew, C. G., Rioux, J. D., Schadt, E. E., Daly, M. J., Franke, A., Parkes, M., Vermeire, S., Barrett, J. C., & Cho, J. H.
- Affiliations
- Wellcome Sanger Institute (GB)
- Broad Institute (US)
- University Medical Center Groningen (NL)
- University of Pittsburgh (US)
- Cedars-Sinai Medical Center (US)
- Yale University (US)
- University of Cambridge (GB)
- Harvard University (US)
- KU Leuven (BE)
- Guy's Hospital (GB)
- Montreal Heart Institute (CA)
- New Jersey Institute of Technology (US)
- Cleveland Clinic (US)
- Peninsula College of Medicine and Dentistry (GB)
- Université Libre de Bruxelles (BE)
- Regionshospitalet Viborg (DK)
- Royal Adelaide Hospital (AU)
- Christian-Albrechts-Universität zu Kiel (DE)
- Flinders University (AU)
- McGill University Health Centre (CA)
- Ludwig-Maximilians-Universität München (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Icahn School of Medicine at Mount Sinai (US)
- University Hospital Bonn (DE)
- Karolinska Institutet (SE)
- Torbay Hospital (GB)
- University of Auckland (NZ)
- Christchurch Hospital (NZ)
- University of Liège (BE)
- Helmholtz Munich (DE)
- St Mark's Hospital (GB)
- Queen's Medical Centre (GB)
- Brigham and Women's Hospital (US)
- Oslo University Hospital (NO)
- Emory University (US)
- Casa Sollievo della Sofferenza (IT)
- Ghent University Hospital (BE)
- The University of Western Australia (AU)
- Western General Hospital (GB)
- Townsville Hospital (AU)
- Newcastle University (GB)
- Ninewells Hospital (GB)
- Manchester Academic Health Science Centre (GB)
- Amsterdam UMC Location University of Amsterdam (NL)
- Royal Hospital for Children (GB)
- St Thomas' Hospital (GB)
- Hospital Clínic de Barcelona (ES)
- QIMR Berghofer Medical Research Institute (AU)
- F. Widjaja Inflammatory Bowel Disease Institute (US)
- Norfolk and Norwich University Hospital (GB)
- Leiden University Medical Center (NL)
- Institut für Humangenetik (DE)
- Mount Sinai Hospital (CA)
- Children's Hospital of Philadelphia (US)
- Johns Hopkins University (US)
- Corresponding author
- Cho, Judy H
- ORCID
- Ripke, Stephan
- Weersma, Rinse K.
- Duerr, Richard H.
- McGovern, Dermot P.
- Hui, Ken Y.
- Lee, James C.
- Sharma, Yashoda
- Anderson, Carl A.
- Ning, Kaida
- Cleynen, Isabelle
- Spain, Sarah L.
- Raychaudhuri, Soumya
- Wei, Zhi
- Abraham, Clara
- Achkar, Jean-Paul
- Ahmad, Tariq
- Amininejad, Leila
- Ananthakrishnan, Ashwin N.
- Andersen, Vibeke
- Andrews, Jane M.
- Baidoo, Leonard
- Bampton, Peter A.
- Bitton, Alain
- Boucher, Gabrielle
- Brand, Stephan
- Cohain, Ariella
- Cichon, Sven
- D’Amato, Mauro
- Dubinsky, Marla
- Edwards, Cathryn
- Ellinghaus, David
- Ferguson, Lynnette R.
- Franchimont, Denis
- Gearry, Richard
- Georges, Michel
- Gieger, Christian
- Haritunians, Talin
- Hart, Ailsa
- Hu, Xinli
- Karlsen, Tom H.
- Kugathasan, Subra
- Latiano, Anna
- Laukens, Debby
- Lees, Charlie W.
- Louis, Edouard
- Mansfield, John
- Mowat, Craig
- Newman, William
- Palmieri, Orazio
- Ponsioen, Cyriel Y.
- Prescott, Natalie J.
- Regueiro, Miguel
- Rotter, Jerome I.
- Russell, Richard K.
- Sanderson, Jeremy D.
- Sans, Miquel
- Schreiber, Stefan
- Simms, Lisa A.
- Targan, Stephan R.
- Taylor, Kent D.
- Verspaget, Hein W.
- Wijmenga, Cisca
- Winkelmann, Juliane
- Xavier, Ramnik J.
- Zeissig, Sebastian
- Zhang, Bin
- Zhao, Hongyu
- Silverberg, Mark S.
- Annese, Vito
- Hakonarson, Hakon
- Brant, Steven R.
- Mathew, Christopher G.
- Rioux, John D.
- Schadt, Eric E.
- Daly, Mark J.
- Parkes, Miles
- Barrett, Jeffrey C.
- Cho, Judy H
- Venue
- Nature
- Published
- 2012-10-31
- Volume
- 491
- Issue
- 7422
- Pages
- 119-124
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3491803
- OpenAlex
- W2143625465
- Cited by
- 4,722
- References
- 30
- Citations by year
- 2026: 169 · 2025: 221 · 2024: 303 · 2023: 296 · 2022: 314 · 2021: 345 · 2020: 360 · 2019: 384 · 2018: 374 · 2017: 404 · 2016: 444 · 2015: 422 · 2014: 424 · 2013: 247 · 2012: 13
- FWCI
- 43.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ResearchOnline at James Cook University (James Cook University) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Lithuanian University of Health Sciences (submittedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- BORIS (University Library Bern) (submittedVersion)
- CLOK (University of Central Lancashire) (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Crohn's and Colitis Foundation of America (DK062422)
- Leona M. and Harry B. Helmsley Charitable Trust
- Wellcome Trust (085475/Z/08/Z, 068545/Z/02), 085475, G0000934, 083948/Z/07/Z, 068545, 089120, 090532, 085475/B/08/Z, 098051)
- Crohn's and Colitis Foundation
- Cedars-Sinai Medical Center
- National Institute for Health and Care Research (NF-SI-0508-10299, NF-SI-0611-10219)
- British Heart Foundation (G0000934)
- Diabetes UK
- King's College London
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Fonds De La Recherche Scientifique - FNRS
- Fonds Wetenschappelijk Onderzoek
- Ministero della Salute
- Örebro Universitet
- Crohn's and Colitis UK (M11-1)
- Karolinska Institutet
- Universitetssjukhuset Örebro
- Svenska Läkaresällskapet
- Exzellenzclusters Entzündungsforschung
- Versus Arthritis (18475)
- National Institutes of Health (G0000934, UL1TR000124, UL1TR000005, 068545/Z/02, M01-RR00425, DK062429, TR000124, RR00425, DK-063491, DK 043351, PO1DK046763)
- U.S. Public Health Service (UL1 TR000124, DK062413, PO1DK046763)
- Inflammatory Bowel and Immunobiology Research Institute
- Medical Research Council (098051, 068545/Z/02, G0000934)
- National Health and Medical Research Council (G0000934)
- Helmholtz Zentrum München
- Münchner Zentrum für Gesundheitswissenschaften
- National Human Genome Research Institute (DK062429, DK062422)
- National Cancer Institute (CA141743, R01CA141743)
- National Institute of General Medical Sciences (T32-GM07205, T32GM007205)
- National Institute of Allergy and Infectious Diseases (AI 062773, R01AI062773)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK076984, DK063491, DK-06-2423, (DK043351, R01DK083756, P01DK046763, DK062429, DK062413, DK062420, R01DK055731, R21DK084554, R03DK076984, DK062429-S1, DK062418, DK 83756, DK062431, DK062422, K23DK097142, DK062432, U01DK062418, DK084554, U01DK062420, M01-RR00425, U01DK062429, U24DK062429, U01DK062413, U01DK062422, P30DK063491, U01DK062432, P30DK043351, U01DK062431, U01DK062423)
- National Institute of Child Health and Human Development
- National Center for Research Resources (M01RR000425, M01-RR00425)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- inflammatory bowel disease, Crohn's disease, ulcerative colitis, host-microbe interactions, mycobacterial infection, immune-mediated diseases, ankylosing spondylitis, psoriasis, genetic susceptibility loci, balancing selection, directional selection, gene co-expression network
- MeSH terms
- Colitis, Ulcerative, Crohn Disease, Haplotypes, Humans, Mycobacterium, Mycobacterium Infections, Mycobacterium tuberculosis, Phenotype, Reproducibility of Results, Inflammatory Bowel Diseases, Genome, Human, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Host-Pathogen Interactions, 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
