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Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Open accessAbstract
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 × 10−7 between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (Pfollow-up ≤ 1.35 × 10−9; Poverall ≤ 1.15 × 10−14), leaving eight regions with small effects or false-positive associations. We also obtained evidence for chromosome 18q22 (Poverall = 1.38 × 10−8) from a GWA study of nonsynonymous SNPs. Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten.
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“Genome-wide association studies have confirmed a number of non-HLA genetic factors that increase the risk of a first appearing b-cell autoantibody or type 1 diabetes, both in first degree relatives of individuals with type 1 diabetes and in the general population (386,387,404,405).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [405]
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“Genomewide association studies have confirmed that the following non-HLA genetic factors increase the risk for type 1 diabetes, both in first-degree relatives of type 1 diabetic patients and in the general population: INS, VNTR, CTLA4, PTPN22, and others (263,265,282,283).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [283]
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Metadata
- Authors
- 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., Field, S. F., Payne, F., Lowe, C. E., Szeszko, J. S., Hafler, J. P., Zeitels, L., Yang, J. H. M., Vella, A., Nutland, S., Stevens, H. E., Schuilenburg, H., Coleman, G., Maisuria, M., Meadows, W., Smink, L. J., Healy, B., Burren, O. S., Lam, A. A. C., Ovington, N. R., Allen, J., Adlem, E., Leung, H.-T., Wallace, C., Howson, J. M. M., Guja, C., Ionescu-Tîrgovişte, C., Simmonds, M. J., Heward, J. M., Gough, S. C. L., Dunger, D. B., Wicker, L. S., & Clayton, D. G.
- Affiliations
- University of Cambridge (GB)
- Mayo Clinic (US)
- Queen Mary University of London (GB)
- University of Birmingham (GB)
- Corresponding author
- Todd, John A
- ORCID
- Todd, John A
- Walker, Neil M
- Cooper, Jason D
- Smyth, Deborah J
- Downes, Kate
- Plagnol, Vincent
- Nejentsev, Sergey
- Payne, Felicity
- Yang, Jennie H M
- Vella, Adrian
- Schuilenburg, Helen
- Burren, Oliver S
- Allen, James
- Wallace, Chris
- Howson, Joanna M M
- Guja, Cristian
- Simmonds, Matthew J
- Dunger, David B
- Wicker, Linda S
- Clayton, David G
- Venue
- Nature Genetics
- Published
- 2007-06-06
- Volume
- 39
- Issue
- 7
- Pages
- 857-864
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2492393
- OpenAlex
- W2014077667
- Semantic Scholar
- 15428b611f4dc565b437064d6d67ac0dfdc439e8
- Cited by
- 1,456
- References
- 32
- Citations by year
- 2026: 13 · 2025: 37 · 2024: 34 · 2023: 28 · 2022: 30 · 2021: 53 · 2020: 53 · 2019: 54 · 2018: 41 · 2017: 51 · 2016: 41 · 2015: 67 · 2014: 87 · 2013: 102 · 2012: 110
- FWCI
- 95.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wellcome Trust (061859/B/00/Z, 061858, 089989)
- Diabetes UK
- 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, genome-wide association study, genetic susceptibility loci, chromosome 12q24, chromosome 12q13, chromosome 16p13, non-synonymous SNPs, autoimmune thyroid disease, Wellcome Trust Case Control Consortium
- MeSH terms
- Adolescent, Chromosome Mapping, Diabetes Mellitus, Type 1, Humans, Genome, Human, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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