The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
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.
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?
In the citing paper
“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.
Citations
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
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
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
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
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 2,113
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
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
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
Intracellular pattern recognition receptors in the host response
Meylan, E., Tschopp, J., & Karin, M. (2006) · Nature · doi:10.1038/nature04946 · Cited by 1,196
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
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
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
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 694
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 573
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 545
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
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 507
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
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 437
Self-citationCordell, H. J., & Clayton, D. G. (2002) · The American Journal of Human Genetics · doi:10.1086/338007 · Cited by 411
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
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
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
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
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 132
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- S. Liuet al., Hum. Mol. Genet.18, 358 (2009).
- We thank the patients control participants and family members for participating in the study. S.N. held the Diabetes Research and Wellness Foundation Non-Clinical Fellowship at the early stages of the project and now holds the Royal Society University Research Fellowship. The Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory is funded by the Juvenile Diabetes Research Foundation the Wellcome Trust and the National Institute for Health Research Biomedical Research Centre. The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (079895). Full acknowledgements are in the supporting online material. Previously unseen SNPs were submitted to dbSNP database (www.ncbi.nlm.nih.gov/SNP/); their submission numbers are in table S3.
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
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
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
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
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
Metadata
- 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
