Rare Variants of IFIH1 , a Gene Implicated in Antiviral Responses, Protect Against Type 1 Diabetes
Open accessAbstract
Genome-wide association studies (GWASs) are regularly used to map genomic regions contributing to common human diseases, but they often do not identify the precise causative genes and sequence variants. To identify causative type 1 diabetes (T1D) variants, we resequenced exons and splice sites of 10 candidate genes in pools of DNA from 480 patients and 480 controls and tested their disease association in over 30,000 participants. We discovered four rare variants that lowered T1D risk independently of each other (odds ratio = 0.51 to 0.74; P = 1.3 × 10 –3 to 2.1 × 10 –16 ) in IFIH1 ( interferon induced with helicase C domain 1 ), a gene located in a region previously associated with T1D by GWASs. These variants are predicted to alter the expression and structure of IFIH1 [MDA5 (melanoma differentiation-associated protein 5)], a cytoplasmic helicase that mediates induction of interferon response to viral RNA. This finding firmly establishes the role of IFIH1 in T1D and demonstrates that resequencing studies can pinpoint disease-causing genes in genomic regions initially identified by GWASs.
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
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?
An initial inflammatory bowel disease screen found rare-variant evidence for just one of 63 GWAS-identified genes.
“only 1 of 63 genes in an initial screen for inflammatory bowel disease found evidence for rare variant effects (and these were protective114, but see also115)”
From Rare and common variants: twenty arguments (2012) · cites this paper as [113]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
Self-citationGenome sequencing in microfabricated high-density picolitre reactors
Margulies, M., Egholm, M., Altman, W. E., Attiya, S., Bader, J. S., Bemben, L. A., Berka, J., Braverman, M. S., Chen, Y.-J., Chen, Z., et al. (2005) · Nature · doi:10.1038/nature03959 · Cited by 7,693 · see citing works
Self-citationDifferential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888 · see citing works
Genome-wide association studies for complex traits: consensus, uncertainty and challenges
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ioannidis, J. P. A., & Hirschhorn, J. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2344 · Cited by 2,891 · see citing works
The impact of next-generation sequencing technology on genetics
Mardis, E. R. (2008) · Trends in Genetics · doi:10.1016/j.tig.2007.12.007 · Cited by 2,050 · see citing works
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Finland, G. O. T. 1. D. I., Todd, J. A., the Wellcome Trust Case Control Consortium, Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., et al. (2007) · Nature Genetics · doi:10.1038/ng2068 · Cited by 1,456 · see citing works
Self-citationGenetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes
Bottini, N., Musumeci, L., Alonso, A., Rahmouni, S., Nika, K., Rostamkhani, M., MacMurray, J. P., Meloni, T., Lucarelli, P., Pellecchia, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1323 · Cited by 1,419 · see citing works
Intracellular pattern recognition receptors in the host response
Meylan, E., Tschopp, J., & Karin, M. (2006) · Nature · doi:10.1038/nature04946 · Cited by 1,196 · see citing works
Common and rare variants in multifactorial susceptibility to common diseases
Bodmer, W., & Bonilla, C. (2008) · Nature Genetics · doi:10.1038/ng.f.136 · Cited by 1,131 · see citing works
Multiple Rare Alleles Contribute to Low Plasma Levels of HDL Cholesterol
Cohen, J. C., Kiss, R. S., Pertsemlidis, A., Marcel, Y. L., McPherson, R., & Hobbs, H. H. (2004) · Science · doi:10.1126/science.1099870 · Cited by 1,108 · see citing works
Rare independent mutations in renal salt handling genes contribute to blood pressure variation
Ji, W., Foo, J. N., O'Roak, B. J., Zhao, H., Larson, M. G., Simon, D. B., Newton-Cheh, C., State, M. W., Levy, D., & Lifton, R. P. (2008) · Nature Genetics · doi:10.1038/ng.118 · Cited by 812 · see citing works
Smyth, D. J., Cooper, J. D., Bailey, R., Field, S., Burren, O. S., Smink, L. J., Guja, C., Ionescu-Tirgoviste, C., Widmer, B., Dunger, D. B., et al. (2006) · Nature Genetics · doi:10.1038/ng1800 · Cited by 688 · see citing works
Self-citationLocalization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A
Nejentsev, S., Howson, J. M. M., Walker, N. M., Szeszko, J. S., Field, S. F., Stevens, H. E., Reynolds, P., Hardy, M. P., King, E., Masters, J., et al. (2007) · Nature · doi:10.1038/nature06406 · Cited by 568 · see citing works
Self-citationMeta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci
Cooper, J. D., Smyth, D. J., Smiles, A. M., Plagnol, V., Walker, N. M., Allen, J. E., Downes, K., Barrett, J. C., Healy, B. C., Mychaleckyj, J. C., et al. (2008) · Nature Genetics · doi:10.1038/ng.249 · Cited by 531 · see citing works
Self-citationRomeo, S., Pennacchio, L. A., Fu, Y., Boerwinkle, E., Tybjaerg-Hansen, A., Hobbs, H. H., & Cohen, J. C. (2007) · Nature Genetics · doi:10.1038/ng1984 · Cited by 511 · see citing works
Smyth, D. J., Cooper, J. D., Collins, J. E., Heward, J. M., Franklyn, J. A., Howson, J. M. M., Vella, A. V., Nutland, S. L., Rance, H. E., Maier, L. M., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.11.3020 · Cited by 504 · see citing works
Self-citationClinical implications of a molecular genetic classification of monogenic β-cell diabetes
Murphy, R., Ellard, S., & Hattersley, A. T. (2008) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0778 · Cited by 502 · see citing works
Lowe, C. E., Cooper, J. D., Brusko, T. M., Walker, N. M., Smyth, D. J., Bailey, R., Bourget, K., Plagnol, V., Field, S., Atkinson, M. A., et al. (2007) · Nature Genetics · doi:10.1038/ng2102 · Cited by 427 · see citing works
Self-citationCordell, H. J., & Clayton, D. G. (2002) · The American Journal of Human Genetics · doi:10.1086/338007 · Cited by 411 · see citing works
The role of viruses in human diabetes
ty, H. H. X. F., & Taylor, K. W. (2002) · Diabetologia · doi:10.1007/s00125-002-0852-3 · Cited by 306 · see citing works
MacMurray, A. J., Moralejo, D. H., Kwitek, A. E., Rutledge, E. A., Yserloo, B. V., Gohlke, P., Speros, S. J., Snyder, B., Schaefer, J. B., Bieg, S., et al. (2002) · Genome Research · doi:10.1101/gr.412702 · Cited by 221 · see citing works
Liu, S., Wang, H., Jin, Y., Podolsky, R. H., Reddy, M. P. L., Pedersen, J. V., Bode, B. W., Reed, J., Steed, D., Anderson, S. W., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn342 · Cited by 160 · see citing works
The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1
Hornum, L., Rømer, J., & Markholst, H. (2002) · Diabetes · doi:10.2337/diabetes.51.6.1972 · Cited by 159 · see citing works
A Human Type 1 Diabetes Susceptibility Locus Maps to Chromosome 21q22.3
CONCANNON, P. J., Önengüt-Gümüşcü, S., Todd, J. A., Smyth, D. J., Pociot, F., Bergholdt, R., Akolkar, B., Erlich, H. A., Hilner, J. E., Julier, C., et al. (2008) · Diabetes · doi:10.2337/db08-0753 · Cited by 131 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [11]Todd JA Nat Genet 2007 39 857 17554260 PMC2492393
- [24]Hyoty H Taylor KW Diabetologia 2002 45 1353 12378375
Cited by
Sorted by citations
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
Finding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336 · see citing works
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
Visscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425 · see citing works
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
DIAGRAM Consortium, Dupuis, J., GIANT Consortium, Global BPgen Consortium, Anders Hamsten on behalf of Procardis Consortium, the MAGIC investigators, Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., et al. (2010) · Nature Genetics · doi:10.1038/ng.520 · Cited by 2,166 · see citing works
Benefits and limitations of genome-wide association studies
Tam, V., Patel, N. K., Turcotte, M., Bossé, Y., Paré, G., & Meyre, D. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0127-1 · Cited by 2,092 · see citing works
Immune Signaling by RIG-I-like Receptors
Loo, Y.-M., & Gale, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.003 · Cited by 1,875 · see citing works
RIG-I-like receptors: their regulation and roles in RNA sensing
Rehwinkel, J., & Gack, M. U. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0288-3 · Cited by 1,703 · see citing works
Fritsche, L. G., Igl, W., Bailey, J. N. C., Grassmann, F., Sengupta, S., Bragg-Gresham, J. L., Burdon, K. P., Hebbring, S. J., Wen, C., Gorski, M., et al. (2016) · Nature Genetics · doi:10.1038/ng.3448 · Cited by 1,544 · see citing works
Genomewide Association Studies and Assessment of the Risk of Disease
Manolio, T. A. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0905980 · Cited by 1,512 · see citing works
The genetics of quantitative traits: challenges and prospects
Mackay, T. F. C., Stone, E. A., & Ayroles, J. F. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2612 · Cited by 1,293 · see citing works
Rare and common variants: twenty arguments
Gibson, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3118 · Cited by 1,278 · see citing works
Genetics, pathogenesis and clinical interventions in type 1 diabetes
Bluestone, J. A., Herold, K., & Eisenbarth, G. (2010) · Nature · doi:10.1038/nature08933 · Cited by 1,265 · see citing works
Uncovering the roles of rare variants in common disease through whole-genome sequencing
Cirulli, E. T., & Goldstein, D. B. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2779 · Cited by 1,136 · see citing works
Lee, S., Emond, M. J., Bamshad, M. J., Barnes, K. C., Rieder, M. J., Nickerson, D. A., Christiani, D. C., Wurfel, M. M., & Lin, X. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.06.007 · Cited by 1,040 · see citing works
Strange, A., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Pirinen, M., Rautanen, A., Su, Z., Donnelly, P., Capon, F., et al. (2010) · Nature Genetics · doi:10.1038/ng.694 · Cited by 1,042 · see citing works
Multiple common variants for celiac disease influencing immune gene expression
Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G., Ádány, R., Aromaa, A. J., et al. (2010) · Nature Genetics · doi:10.1038/ng.543 · Cited by 1,026 · see citing works
Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies
Van Belle, T. L., Coppieters, K. T., & Von Herrath, M. G. (2011) · Physiological Reviews · doi:10.1152/physrev.00003.2010 · Cited by 1,022 · see citing works
Rare Variants Create Synthetic Genome-Wide Associations
Dickson, S. P., Wang, K., Krantz, I., Hakonarson, H., & Goldstein, D. B. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000294 · Cited by 857 · see citing works
The Genetics of Alzheimer Disease: Back to the Future
Bertram, L., Lill, C. M., & Tanzi, R. E. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.013 · Cited by 834 · see citing works
The Genetics of Alzheimer's Disease
Bertram, L., & Tanzi, R. E. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00008-4 · Cited by 784 · see citing works
Seven new loci associated with age-related macular degeneration
The AMD Gene Consortium (2013) · Nature Genetics · doi:10.1038/ng.2578 · Cited by 788 · see citing works
National Institute of Diabetes and Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium (NIDDK IBDGC), Rivas, M. A., United Kingdom Inflammatory Bowel Disease Genetics Consortium, International Inflammatory Bowel Disease Genetics Consortium, Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C. K., Boucher, G., et al. (2011) · Nature Genetics · doi:10.1038/ng.952 · Cited by 771 · see citing works
Pooled Association Tests for Rare Variants in Exon-Resequencing Studies
Price, A. L., Kryukov, G. V., de Bakker, P. I. W., Purcell, S. M., Staples, J., Wei, L.-J., & Sunyaev, S. R. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.04.005 · Cited by 755 · see citing works
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 · see citing works
Common vs. rare allele hypotheses for complex diseases
Schork, N. J., Murray, S. S., Frazer, K. A., & Topol, E. J. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.04.010 · Cited by 649 · see citing works
Fine-mapping inflammatory bowel disease loci to single-variant resolution
International Inflammatory Bowel Disease Genetics Consortium, Huang, H., Fang, M., Jostins, L., Umićević Mirkov, M., Boucher, G., Anderson, C. A., Andersen, V., Cleynen, I., Cortes, A., et al. (2017) · Nature · doi:10.1038/nature22969 · Cited by 611 · see citing works
A survey of tools for variant analysis of next-generation genome sequencing data
Pabinger, S., Dander, A., Fischer, M., Snajder, R., Sperk, M., Efremova, M., Krabichler, B., Speicher, M. R., Zschocke, J., & Trajanoski, Z. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs086 · Cited by 595 · see citing works
Rice, G., Duany, Y. D. T., Jenkinson, E. M., Forte, G. M. A., Anderson, B., Ariaudo, G., Bader‐Meunier, B., Baildam, E. M., Battini, R., Beresford, M. W., et al. (2014) · Nature Genetics · doi:10.1038/ng.2933 · Cited by 593 · see citing works
Statistical power and significance testing in large-scale genetic studies
Sham, P. C., & Purcell, S. M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3706 · Cited by 573 · see citing works
Todd, J. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.04.001 · Cited by 560 · see citing works
Self-citationGenetic insights into common pathways and complex relationships among immune-mediated diseases
Parkes, M., Cortés, A., van Heel, D. A., & Brown, M. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3502 · Cited by 522 · see citing works
Pestal, K., Funk, C. C., Snyder, J. M., Price, N. D., Treuting, P. M., & Stetson, D. B. (2015) · Immunity · doi:10.1016/j.immuni.2015.11.001 · Cited by 516 · see citing works
The heterogeneous pathogenesis of type 1 diabetes mellitus
Ilonen, J., Lempainen, J., & Veijola, R. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0254-y · Cited by 496 · see citing works
Loss-of-function mutations in SLC30A8 protect against type 2 diabetes
Go-T2D Consortium, Flannick, J., T2D-GENES Consortium, Thorleifsson, G., Beer, N. L., Jacobs, S. B. R., Grarup, N., Burtt, N. P., Mahajan, A., Fuchsberger, C., et al. (2014) · Nature Genetics · doi:10.1038/ng.2915 · Cited by 492 · see citing works
Immune cell crosstalk in type 1 diabetes
Lehuen, A., Diana, J., Zaccone, P., & Cooke, A. (2010) · Nature reviews. Immunology · doi:10.1038/nri2787 · Cited by 478 · see citing works
Statistical analysis strategies for association studies involving rare variants
Bansal, V., Libiger, O., Torkamani, A., & Schork, N. J. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2867 · Cited by 455 · see citing works
Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia
Johansen, C. T., Wang, J., Lanktree, M. B., Cao, H., McIntyre, A. D., Ban, M. R., Martins, R. A., Kennedy, B. A., Hassell, R. G., Visser, M. E., et al. (2010) · Nature Genetics · doi:10.1038/ng.628 · Cited by 437 · see citing works
Matsuo, H., Takada, T., Ichida, K., Nakamura, T., Nakayama, A., Ikebuchi, Y., Ito, K., Kusanagi, Y., Chiba, T., Tadokoro, S., et al. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000237 · Cited by 437 · see citing works
Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors
Onomoto, K., Onoguchi, K., & Yoneyama, M. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00602-7 · Cited by 432 · see citing works
The genetic contribution to non-syndromic human obesity
Walley, A. J., Asher, J. E., & Froguel, P. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2594 · Cited by 402 · see citing works
Genetics and epigenetics of rheumatoid arthritis
Viatte, S., Plant, D., & Raychaudhuri, S. (2013) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.237 · Cited by 399 · see citing works
GATES: A Rapid and Powerful Gene-Based Association Test Using Extended Simes Procedure
Li, M., Gui, H., Kwan, J. S. H., & Sham, P. C. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.01.019 · Cited by 386 · see citing works
Differential confounding of rare and common variants in spatially structured populations
Mathieson, I., & McVean, G. (2012) · Nature Genetics · doi:10.1038/ng.1074 · Cited by 385 · see citing works
Exome sequencing and the genetic basis of complex traits
Kiezun, A., Garimella, K., Do, R., Stitziel, N. O., Neale, B. M., McLaren, P. J., Gupta, N., Sklar, P., Sullivan, P. F., Moran, J. L., et al. (2012) · Nature Genetics · doi:10.1038/ng.2303 · Cited by 372 · see citing works
Casanova, J., Abel, L., & Quintana‐Murci, L. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101335 · Cited by 369 · see citing works
Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes
The Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC), Bonnefond, A., Clément, N., Fawcett, K., Yengo, L., Vaillant, E., Guillaume, J.-L., Dechaume, A., Payne, F., Roussel, R., et al. (2012) · Nature Genetics · doi:10.1038/ng.1053 · Cited by 363 · see citing works
Genomics and the Multifactorial Nature of Human Autoimmune Disease
Cho, J. H., & Gregersen, P. K. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1100030 · Cited by 349 · see citing works
Noble, J. A., & Erlich, H. A. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007732 · Cited by 335 · see citing works
The enemy within: endogenous retroelements and autoimmune disease
Volkman, H. E., & Stetson, D. B. (2014) · Nature Immunology · doi:10.1038/ni.2872 · Cited by 333 · see citing works
Cruchaga, C., Chakraverty, S., Mayo, K., Vallania, F. L. M., Mitra, R. D., Faber, K., Williamson, J., Bird, T., Diaz-Arrastia, R., Foroud, T. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031039 · Cited by 320 · see citing works
A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation
Dias, A. G., Sampaio, N. G., & Rehwinkel, J. (2018) · Trends in Microbiology · doi:10.1016/j.tim.2018.08.007 · Cited by 309 · see citing works
CHARGE-Heart Failure Consortium, Surendran, P., EchoGen Consortium, METASTROKE Consortium, GIANT Consortium, EPIC-InterAct Consortium, Study, L. C., Wellcome Trust Case Control Consortium, Understanding Society Scientific Group, EPIC-CVD Consortium, et al. (2016) · Nature Genetics · doi:10.1038/ng.3654 · Cited by 312 · see citing works
Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition
Peisley, A., Lin, C., Wu, B., Orme-Johnson, M., Liu, M., Walz, T., & Hur, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113651108 · Cited by 312 · see citing works
Genomics of disease risk in globally diverse populations
Gurdasani, D., Barroso, I., Zeggini, E., & Sandhu, M. S. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0144-0 · Cited by 299 · see citing works
Recognition of viral nucleic acids in innate immunity
Yoneyama, M., & Fujita, T. (2009) · Reviews in Medical Virology · doi:10.1002/rmv.633 · Cited by 303 · see citing works
Holmen, O. L., Zhang, H., Fan, Y., Hovelson, D. H., Schmidt, E. M., Zhou, W., Guo, Y., Zhang, J., Langhammer, A., Løchen, M., et al. (2014) · Nature Genetics · doi:10.1038/ng.2926 · Cited by 302 · see citing works
Genetics of Type 1 Diabetes: What's Next?
Pociot, F., Akolkar, B., CONCANNON, P. J., Erlich, H. A., Julier, C., Morahan, G., Nierras, C. R., Todd, J. A., Rich, S. S., & Nerup, J. (2010) · Diabetes · doi:10.2337/db10-0076 · Cited by 302 · see citing works
Self-citationA POPULATION-SPECIFIC HTR2B STOP CODON PREDISPOSES TO SEVERE IMPULSIVITY
Bevilacqua, L., Doly, S., Kaprio, J., Yuan, Q., Tikkanen, R., Paunio, T., Zhou, Z.-F., Wedenoja, J., Maroteaux, L., Diaz, S., et al. (2010) · Nature · doi:10.1038/nature09629 · Cited by 321 · see citing works
Viral infections in type 1 diabetes mellitus — why the β cells?
Op de Beeck, A., & Eizirik, D. L. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.30 · Cited by 291 · see citing works
Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity
Crow, Y. J., & Rehwinkel, J. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp293 · Cited by 289 · see citing works
A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
Cardiogenics Consortium, Heinig, M., Petretto, E., Wallace, C., Bottolo, L., Rotival, M., Lu, H., Li, Y., Sarwar, R., Langley, S. R., et al. (2010) · Nature · doi:10.1038/nature09386 · Cited by 283 · see citing works
Self-citationYi, G., Brendel, V., Shu, C., Li, P., Palanathan, S., & Kao, C. C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077846 · Cited by 274 · see citing works
A General Framework for Detecting Disease Associations with Rare Variants in Sequencing Studies
Lin, D.-Y., & Tang, Z.-Z. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.07.015 · Cited by 274 · see citing works
Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host
Hober, D., & Sauter, P. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.27 · Cited by 271 · see citing works
Galarneau, G., Palmer, C. D., Sankaran, V. G., Orkin, S. H., Hirschhorn, J. N., & Lettre, G. (2010) · Nature Genetics · doi:10.1038/ng.707 · Cited by 267 · see citing works
Rare Variant Association Analysis Methods for Complex Traits
Asimit, J. L., & Zeggini, E. (2010) · Annual Review of Genetics · doi:10.1146/annurev-genet-102209-163421 · Cited by 267 · see citing works
Autoimmune Disorders Associated with Gain of Function of the Intracellular Sensor MDA5
Funabiki, M., Kato, H., Miyachi, Y., Toki, H., Motegi, H., Inoue, M., Minowa, O., Yoshida, A., Deguchi, K., Satō, H., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.12.014 · Cited by 262 · see citing works
On type 1 diabetes mellitus pathogenesis
Paschou, S. Α., Papadopoulou‐Marketou, N., Chrousos, G. P., & Kanaka‐Gantenbein, C. (2017) · Endocrine Connections · doi:10.1530/ec-17-0347 · Cited by 263 · see citing works
Autoimmune diseases — connecting risk alleles with molecular traits of the immune system
Gutiérrez‐Arcelus, M., Rich, S. S., & Raychaudhuri, S. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.33 · Cited by 254 · see citing works
Wei, Z., Wang, W., Hu, P., Lyon, G. J., & Hakonarson, H. H. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr599 · Cited by 253 · see citing works
Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis
Möller, M., & Hoal, E. G. (2010) · Tuberculosis · doi:10.1016/j.tube.2010.02.002 · Cited by 229 · see citing works
Pattern recognition receptors in innate immunity, host defense, and immunopathology
Suresh, R., & Mosser, D. M. (2013) · AJP Advances in Physiology Education · doi:10.1152/advan.00058.2013 · Cited by 229 · see citing works
Understanding type 1 diabetes through genetics: advances and prospects
Polychronakos, C., & Li, Q. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3069 · Cited by 226 · see citing works
A Specific IFIH1 Gain-of-Function Mutation Causes Singleton-Merten Syndrome
Rutsch, F., MacDougall, M. J., Lu, C., Buers, I., Mamaeva, O. A., Nitschke, Y., Rice, G., Erlandsen, H., Kehl, H.-G., Thiele, H., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.12.014 · Cited by 226 · see citing works
Intracellular Nucleic Acid Detection in Autoimmunity
Crowl, J. T., Gray, E. E., Pestal, K., Volkman, H. E., & Stetson, D. B. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052331 · Cited by 216 · see citing works
A large-scale screen for coding variants predisposing to psoriasis
Tang, H., Jin, X., Li, Y., Jiang, H., Tang, X., Yang, X., Cheng, H., Qiu, Y., Chen, G., Mei, J., et al. (2013) · Nature Genetics · doi:10.1038/ng.2827 · Cited by 219 · see citing works
Vecchio, F., Buono, N. L., Stabilini, A., Nigi, L., Dufort, M. J., Geyer, S. M., Rancoita, P. M. V., Cugnata, F., Mandelli, A., Valle, A., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.122146 · Cited by 219 · see citing works
MDA5 cooperatively forms dimers and ATP‐sensitive filaments upon binding double‐stranded RNA
Berke, I. C., & Modis, Y. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.19 · Cited by 205 · see citing works
Metagenomics and Personalized Medicine
Virgin, H. W., & Todd, J. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.009 · Cited by 203 · see citing works
Self-citationSelective IgA Deficiency in Autoimmune Diseases
Wang, N., Shen, N., Vyse, T. J., Anand, V., Gunnarson, I., Sturfelt, G. K., Rantapää‐Dahlqvist, S., Elvin, K., Truedsson, L., Andersson, B. A., et al. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00195 · Cited by 205 · see citing works
The Virome in Host Health and Disease
Cadwell, K. (2015) · Immunity · doi:10.1016/j.immuni.2015.05.003 · Cited by 202 · see citing works
Momozawa, Y., Mni, M., Nakamura, K., Coppieters, W., Almer, S., Amininejad, L., Cleynen, I., Colombel, J.-F., de Rijk, P., Dewit, O., et al. (2011) · Nature Genetics · doi:10.1038/ng.733 · Cited by 189 · see citing works
Genome-wide association studies in mice
Flint, J., & Eskin, E. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3335 · Cited by 188 · see citing works
RNA editing underlies genetic risk of common inflammatory diseases
Li, Q., Gloudemans, M. J., Geisinger, J. M., Fan, B., Aguet, F., Sun, T., Ramaswami, G., Li, Y., Ma, J., Pritchard, J. K., et al. (2022) · Nature · doi:10.1038/s41586-022-05052-x · Cited by 187 · see citing works
A statistical method for the detection of variants from next-generation resequencing of DNA pools
Bansal, V. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq214 · Cited by 186 · see citing works
Negligible impact of rare autoimmune-locus coding-region variants on missing heritability
Hunt, K. A., Mistry, V., Bockett, N. A., Ahmad, T., Ban, M., Barker, J. N., Barrett, J. C., Blackburn, H., Brand, O. J., Burren, O. S., et al. (2013) · Nature · doi:10.1038/nature12170 · Cited by 184 · see citing works
Self-citationThe pursuit of genome-wide association studies: where are we now?
Ku, C., Loy, E. Y., Yudi Pawitan, Y., & Chia, K. S. (2010) · Journal of Human Genetics · doi:10.1038/jhg.2010.19 · Cited by 181 · see citing works
van de Bunt, M., Fox, J. E. M., Dai, X.-Q., Barrett, A., Grey, C. L., Li, L., Bennett, A. J., Johnson, P. R. V., Rajotte, R. V., Gaulton, K. J., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005694 · Cited by 174 · see citing works
Zhan, X., Larson, D. E., Wang, C., Koboldt, D. C., Sergeev, Y. V., Fulton, R. S., Fulton, L., Fronick, C. C., Branham, K. E. H., Bragg‐Gresham, J. L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2758 · Cited by 177 · see citing works
King, E. G., Macdonald, S. J., & Long, A. D. (2012) · Genetics · doi:10.1534/genetics.112.138537 · Cited by 175 · see citing works
Genetic architecture of colorectal cancer
Peters, U., Bien, S. A., & Zubair, N. (2015) · Gut · doi:10.1136/gutjnl-2013-306705 · Cited by 175 · see citing works
Genetics of autoimmune diseases: Insights from population genetics
Ramos, P. S., Shedlock, A. M., & Langefeld, C. D. (2015) · Journal of Human Genetics · doi:10.1038/jhg.2015.94 · Cited by 173 · see citing works
Fukui, T., Kobayashi, T., Jimbo, E., Aida, K., Shimada, A., Oikawa, Y., Mori, Y., Fujii, T., Koyama, R., Kobayashi, K., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-33011-7 · Cited by 164 · see citing works
The 1000 Genomes Project: new opportunities for research and social challenges
Vía, M., Gignoux, C. R., & Burchard, E. G. (2010) · Genome Medicine · doi:10.1186/gm124 · Cited by 163 · see citing works
Functionally defective germline variants of sialic acid acetylesterase in autoimmunity
Surolia, I., Pirnie, S. P., Chellappa, V., Taylor, K. N., Cariappa, A., Moya, J., Liu, H., Bell, D. W., Driscoll, D. R., Diederichs, S., et al. (2010) · Nature · doi:10.1038/nature09115 · Cited by 162 · see citing works
MDA5 and MAVS Mediate Type I Interferon Responses to Coxsackie B Virus
Wang, J. P., Cerny, A., Asher, D. R., Kurt‐Jones, E. A., Bronson, R. T., & Finberg, R. W. (2009) · Journal of Virology · doi:10.1128/jvi.00631-09 · Cited by 161 · see citing works
A method for counting PCR template molecules with application to next-generation sequencing
Casbon, J. A., Osborne, R. J., Brenner, S., & Lichtenstein, C. P. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr217 · Cited by 158 · see citing works
Identification of Loss of Function Mutations in Human Genes Encoding RIG-I and MDA5
Shigemoto, T., Kageyama, M., Hirai, R., Zheng, J., Yoneyama, M., & Fujita, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809449200 · Cited by 161 · see citing works
Kirino, Y., Zhou, Q., Ishigatsubo, Y., Mizuki, N., Tuğal-Tutkun, İ., Seyahi, E., Özyazgan, Y., Uğurlu, S., Erer, B., Abacı, N., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1306352110 · Cited by 161 · see citing works
- Authors
- Nejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Nejentsev, Sergey
- Venue
- Science
- Published
- 2009-04-17
- Volume
- 324
- Issue
- 5925
- Pages
- 387-389
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2707798
- OpenAlex
- W2020040634
- Cited by
- 958
- References
- 25
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 11 · 2023: 25 · 2022: 22 · 2021: 29 · 2020: 30 · 2019: 30 · 2018: 27 · 2017: 47 · 2016: 36 · 2015: 72 · 2014: 72 · 2013: 109 · 2012: 115
- FWCI
- 82.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wellcome Trust (061858, 079895)
- National Institute for Health and Care Research (NF-SI-0508-10275)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- type 1 diabetes, MDA5, rare variants, antiviral response, interferon induction, viral RNA sensing, disease-associated genes, genetic risk
- MeSH terms
- Interferon-Induced Helicase, IFIH1, Base Sequence, Diabetes Mellitus, Type 1, Gene Frequency, Humans, Molecular Sequence Data, Risk, Risk Factors, Genetic Variation, Linkage Disequilibrium, Case-Control Studies, Sequence Analysis, DNA, Codon, Nonsense, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, RNA Splice Sites, DEAD-box RNA Helicases, 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
