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A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene
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.
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“Genome-wide association studies (GWAS) demonstrate that alleles of the CLEC16A gene (also KIAA0350) confer risk for autoimmune diseases including type 1 diabetes, multiple sclerosis, primary adrenal insufficiency, primary biliary cirrhosis, alopecia areata, juvenile idiopathic arthritis and rheumatoid arthritis1234567.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [2]
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Metadata
- 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
- Venue
- Nature
- Published
- 2007-07-15
- Volume
- 448
- Issue
- 7153
- Pages
- 591-594
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
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