Cited by 542Diabetes and associated disordersGenetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and Animals

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene

Hakonarson, Hakon, Grant, Struan F. A., Bradfield, Jonathan P., Marchand, Luc, Kim, Cecilia E., Glessner, Joseph T., Grabs, Rosemarie, Casalunovo, Tracy, Taback, Shayne P., Frackelton, Edward C., Lawson, Margaret L., Robinson, Luke J., Skraban, Robert, Lu, Yang, Chiavacci, Rosetta M., Stanley, Charles A., Kirsch, Susan E., Rappaport, Eric F., Orange, Jordan S., Monos, Dimitri S., Devoto, Marcella, Qu, Hui-Qi, Polychronakos, Constantin·2007·Nature

DOI 10.1038/nature06010

Open this paper in CoChat — free account

Abstract

Type 1 diabetes (T1D) in children results from autoimmune destruction of pancreatic beta cells, leading to insufficient production of insulin. A number of genetic determinants of T1D have already been established through candidate gene studies, primarily within the major histocompatibility complex but also within other loci. To identify new genetic factors that increase the risk of T1D, we performed a genome-wide association study in a large paediatric cohort of European descent. In addition to confirming previously identified loci, we found that T1D was significantly associated with variation within a 233-kb linkage disequilibrium block on chromosome 16p13. This region contains KIAA0350, the gene product of which is predicted to be a sugar-binding, C-type lectin. Three common non-coding variants of the gene (rs2903692, rs725613 and rs17673553) in strong linkage disequilibrium reached genome-wide significance for association with T1D. A subsequent transmission disequilibrium test replication study in an independent cohort confirmed the association. These results indicate that KIAA0350 might be involved in the pathogenesis of T1D and demonstrate the utility of the genome-wide association approach in the identification of previously unsuspected genetic determinants of complex traits.

Integrity signals

Registry

Crossref · 10.1038/nature06010

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

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

Claims the paper makes

This paper’s full text isn’t openly available, 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?

PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth457 · Cited by 14,551
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
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
Pfam: clans, web tools and services
Finn, R. D. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj149 · Cited by 2,291
Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
Ueda, H., Howson, J. M. M., Esposito, L., Heward, J., Snook, Chamberlain, G., Rainbow, D. B., Hunter, K. M. D., Smith, A. N., Di Genova, G., et al. (2003) · Nature · doi:10.1038/nature01621 · Cited by 2,175
A comprehensive review of genetic association studies
Hirschhorn, J. N., Lohmueller, K., Byrne, E., & Hirschhorn, K. (2002) · Genetics in Medicine · doi:10.1097/00125817-200203000-00002 · Cited by 1,674
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
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
A genome-wide search for human type 1 diabetes susceptibility genes
Davies, J. L., Kawaguchi, Y., Bennett, S. T., Copeman, J. B., Cordell, H. J., Pritchard, L. E., Reed, P. W., Gough, S. C. L., Jenkins, S. C., Palmer, S. M., et al. (1994) · Nature · doi:10.1038/371130a0 · Cited by 1,276
HL-A ANTIGENS AND DIABETES MELLITUS
Nerup, J., Platz, P., Andersen, O. O., Christy, M., LYNGSØE, J., Poulsen, J. E., Ryder, L. P., Thomsen, M., Nielsen, L. S., & Svejgaard, A. (1974) · The Lancet · doi:10.1016/s0140-6736(74)91201-x · Cited by 823
Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus
Vafiadis, P., Bennett, S. T., Todd, J. A., Nadeau, J., Grabs, R., Goodyer, C. G., Wickramasinghe, S., Colle, E., & Polychronakos, C. (1997) · Nature Genetics · doi:10.1038/ng0397-289 · Cited by 809
Self-citation
A Polymorphic Locus Near the Human Insulin Gene Is Associated with Insulin-dependent Diabetes Melliitus
Bell, G. I., Horita, S., & Karam, J. H. (1984) · Diabetes · doi:10.2337/diab.33.2.176 · Cited by 779
A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC
de Bakker, P. I. W., McVean, G., Sabeti, P. C., Miretti, M. M., Green, T., Marchini, J., Ke, X., Monsuur, A. J., Whittaker, P., Delgado, M., et al. (2006) · Nature Genetics · doi:10.1038/ng1885 · Cited by 766
Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus
Bennett, S. T., Lucassen, A. M., Gough, S. C. L., Powell, E. E., Undlien, D. E., Pritchard, L. E., Merriman, M. E., Kawaguchi, Y., Dronsfield, M. J., Pociot, F., et al. (1995) · Nature Genetics · doi:10.1038/ng0395-284 · Cited by 746
A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region
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
A genome-wide scalable SNP genotyping assay using microarray technology
Gunderson, K., Steemers, F. J., Lee, G., Mendoza, L. G., & Chee, M. (2005) · Nature Genetics · doi:10.1038/ng1547 · Cited by 665
Replication of an Association Between the Lymphoid Tyrosine Phosphatase Locus (LYP/PTPN22) With Type 1 Diabetes, and Evidence for Its Role as a General Autoimmunity Locus
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
The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families.
Noble, J. A., Valdes, A. M., Cook, M., Klitz, W., Thomson, G., & Erlich, H. A. (1996) · PubMed Central · Cited by 481
A functional variant of SUMO4, a new IκBα modifier, is associated with type 1 diabetes
Guo, D., Li, M., Zhang, Y., Yang, P. C., Eckenrode, S., Hopkins, D., Zheng, W., Purohit, S. B., Podolsky, R. H., MUIR, A. B., et al. (2004) · Nature Genetics · doi:10.1038/ng1391 · Cited by 431
CTLA-4 in autoimmune diseases – a general susceptibility gene to autoimmunity?
Kristiansen, O., Larsen, Z., & Pociot, F. (2000) · Genes and Immunity · doi:10.1038/sj.gene.6363655 · Cited by 414
Whole-genome genotyping with the single-base extension assay
Steemers, F. J., Chang, W., Lee, G., Barker, D. L. A., Shen, R., & Gunderson, K. L. (2005) · Nature Methods · doi:10.1038/nmeth842 · Cited by 378
Localization of a Type 1 Diabetes Locus in the IL2RA/CD25 Region by Use of Tag Single-Nucleotide Polymorphisms
Vella, A. V., Cooper, J. D., Lowe, C. E., Walker, N. M., Nutland, S. L., Widmer, B., Jones, R. W., Ring, S. M., McArdle, W. L., Pembrey, M. E., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/429843 · Cited by 363
Type 1 diabetes: recent developments
Devendra, D., Liu, E., & Eisenbarth, G. S. (2004) · BMJ · doi:10.1136/bmj.328.7442.750 · Cited by 362
A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus
CONCANNON, P. J., Gogolin-Ewens, K. J., Hinds, D. A., Wapelhorst, B., Morrison, V. A., Stirling, B., Mitra, M., Farmer, J. M., Williams, S. R., Cox, N. J., et al. (1998) · Nature Genetics · doi:10.1038/985 · Cited by 336
A search for type 1 diabetes susceptibility genes in families from the United Kingdom
Mein, C. A., Esposito, L., Dunn, M. G., Johnson, G. C. L., Timms, A. E., Goy, J. V., Smith, A. N., Sebag‐Montefiore, L., Merriman, M. E., Wilson, A., et al. (1998) · Nature Genetics · doi:10.1038/991 · Cited by 327
A correlation between the relative predisposition of MHC class II alleles to type 1 diabetes and the structure of their proteins.
Cucca, F., Lampis, R., Congia, M., Angius, E., Nutland, S., Bain, S., Barnett, A., & Todd, J. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.19.2025 · Cited by 202
Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity
Poirot, L., Benoist, C. O., & Mathis, D. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402065101 · Cited by 182
Altered Natural Killer Cells in Type 1 Diabetic Patients
Rodacki, M., Svoren, B. M., Butty, V. L., Besse, W., Laffel, L. M., Benoist, C. O., & Mathis, D. J. (2006) · Diabetes · doi:10.2337/db06-0493 · Cited by 163
A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients
Cucca, F., Goy, J. V., Kawaguchi, Y., Esposito, L., Merriman, M. E., Wilson, A., Cordell, H. J., Bain, S. C., & Todd, J. A. (1998) · Nature Genetics · doi:10.1038/995 · Cited by 128
Levels of complexity in pathogen recognition by C-type lectins
Cambi, A., & Figdor, C. G. (2005) · Current Opinion in Immunology · doi:10.1016/j.coi.2005.05.011 · Cited by 80
Association of IL4R Haplotypes With Type 1 Diabetes
Mirel, D. B., Valdes, A. M., Lazzeroni, L. C., Reynolds, R., Erlich, H. A., & Noble, J. A. (2002) · Diabetes · doi:10.2337/diabetes.51.11.3336 · Cited by 70
Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity
Biason‐Lauber, A., Boehm, B. O., Lang‐Muritano, M., Gauthier, B. R., Brun, T., Wollheim, C. B., & Schoenle, E. J. (2005) · Diabetologia · doi:10.1007/s00125-005-1723-5 · Cited by 69
Association of the Cytotoxic T Lymphocyte-Associated Antigen 4 Gene with Type 1 Diabetes: Evidence for Independent Effects of Two Polymorphisms on the Same Haplotype Block
Anjos, S. M., Tessier, M.-C., & Polychronakos, C. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0881 · Cited by 69
Self-citation

Flagged first, then by citations

Research works printed but not linked: 1

Purcell, S. et al. PLINK: a toolset for whole-genome association and population-based linkage analysis. Am. J. Hum. Genet. (in the press)

Sorted by citations

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
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
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes
The Type 1 Diabetes Genetics Consortium, Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.381 · Cited by 1,746
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
How to Interpret a Genome-wide Association Study
Pearson, T. A. (2008) · JAMA · doi:10.1001/jama.299.11.1335 · Cited by 1,005

See all 542

Authors: Hakonarson, H., Grant, S. F. A., Bradfield, J. P., Marchand, L., Kim, C. E., Glessner, J. T., Grabs, R., Casalunovo, T., Taback, S. P., Frackelton, E. C., Lawson, M. L., Robinson, L. J., Skraban, R., Lu, Y., Chiavacci, R. M., Stanley, C. A., Kirsch, S. E., Rappaport, E. F., Orange, J. S., Monos, D. S., Devoto, M., Qu, H.-Q., & Polychronakos, C.
Affiliations: Children's Hospital of Philadelphia (US)
Pediatrics and Genetics (US)
Centre for Applied Genomics (CA)
McGill University (CA)
University of Manitoba (CA)
University of Ottawa (CA)
Markham Stouffville Hospital (CA)
University of Pennsylvania (US)
Corresponding author: Hakonarson, Hakon
Polychronakos, Constantin
ORCID: Hakonarson, Hakon
Grant, Struan F. A.
Glessner, Joseph T.
Lawson, Margaret L.
Lu, Yang
Stanley, Charles A.
Kirsch, Susan E.
Orange, Jordan S.
Monos, Dimitri S.
Devoto, Marcella
Qu, Hui-Qi
Polychronakos, Constantin
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2007-07-15
Volume: 448
Issue: 7153
Pages: 591-594
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature06010
OpenAlex: W2031539362
Cited by: 542
References: 34
Citations by year: 2026: 8 · 2025: 9 · 2024: 14 · 2023: 7 · 2022: 16 · 2021: 26 · 2020: 13 · 2019: 16 · 2018: 14 · 2017: 18 · 2016: 22 · 2015: 22 · 2014: 28 · 2013: 40 · 2012: 25
FWCI: 39.45
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords: type 1 diabetes, C-type lectin, sugar-binding proteins, genetic susceptibility, chromosome 16p13, linkage disequilibrium, non-coding variants, transmission disequilibrium test, pediatric diabetes, major histocompatibility complex, islet autoimmunity
MeSH terms: Diabetes Mellitus, Type 1, Genetic Markers, Humans, Monosaccharide Transport Proteins, Nuclear Family, Cohort Studies, Linkage Disequilibrium, Genome, Human, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Lectins, C-Type

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

A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks