The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age.
<h4>Aims/hypothesis</h4> <p>The genetic risk of type 1 diabetes has been extensively studied. However, the genetic determinants of age at diagnosis (AAD) of type 1 diabetes remain relatively unexplained. Identification of AAD genes and pathways could provide insight into the earli...
| Main Authors: | , , , , |
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| 格式: | Journal article |
| 語言: | English |
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Springer
2017
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| _version_ | 1826272399490809856 |
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| author | Inshaw, J Walker, N Wallace, C Bottolo, L Todd, J |
| author_facet | Inshaw, J Walker, N Wallace, C Bottolo, L Todd, J |
| author_sort | Inshaw, J |
| collection | OXFORD |
| description | <h4>Aims/hypothesis</h4> <p>The genetic risk of type 1 diabetes has been extensively studied. However, the genetic determinants of age at diagnosis (AAD) of type 1 diabetes remain relatively unexplained. Identification of AAD genes and pathways could provide insight into the earliest events in the disease process.</p> <h4>Methods</h4> <p>Using ImmunoChip data from 15,696 cases, we aimed to identify regions in the genome associated with AAD.</p> <h4>Results</h4> <p>Two regions were convincingly associated with AAD (p < 5 × 10^−8): the MHC on 6p21, and 6q22.33. Fine-mapping of 6q22.33 identified two AAD-associated haplotypes in the region nearest to the genes encoding protein tyrosine phosphatase receptor kappa (PTPRK) and thymocyte-expressed molecule involved in selection (THEMIS).We examined the susceptibility to type 1 diabetes at these SNPs by performing a metaanalysis including 19,510 control participants. Although these SNPs were not associated with type 1 diabetes overall (p > 0.001), the SNP most associated with AAD, rs72975913, was associated with susceptibility to type 1 diabetes in those individuals diagnosed at less than 5 years old (p = 2.3 × 10^−9).</p> <h4>Conclusion/interpretation</h4> <p>PTPRK and its neighbour THEMIS are required for early development of the thymus, which we can assume influences the initiation of autoimmunity. Non-HLA genes may only be detectable as risk factors for the disease in individuals diagnosed under the age 5 years because, after that period of immune development, their role in disease susceptibility has become redundant.</p> |
| first_indexed | 2024-03-06T22:11:58Z |
| format | Journal article |
| id | oxford-uuid:521d4ba7-aeeb-46a7-a0a6-2cddf5a54cc2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:11:58Z |
| publishDate | 2017 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:521d4ba7-aeeb-46a7-a0a6-2cddf5a54cc22022-03-26T16:23:39ZThe chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:521d4ba7-aeeb-46a7-a0a6-2cddf5a54cc2EnglishSymplectic Elements at OxfordSpringer2017Inshaw, JWalker, NWallace, CBottolo, LTodd, J <h4>Aims/hypothesis</h4> <p>The genetic risk of type 1 diabetes has been extensively studied. However, the genetic determinants of age at diagnosis (AAD) of type 1 diabetes remain relatively unexplained. Identification of AAD genes and pathways could provide insight into the earliest events in the disease process.</p> <h4>Methods</h4> <p>Using ImmunoChip data from 15,696 cases, we aimed to identify regions in the genome associated with AAD.</p> <h4>Results</h4> <p>Two regions were convincingly associated with AAD (p < 5 × 10^−8): the MHC on 6p21, and 6q22.33. Fine-mapping of 6q22.33 identified two AAD-associated haplotypes in the region nearest to the genes encoding protein tyrosine phosphatase receptor kappa (PTPRK) and thymocyte-expressed molecule involved in selection (THEMIS).We examined the susceptibility to type 1 diabetes at these SNPs by performing a metaanalysis including 19,510 control participants. Although these SNPs were not associated with type 1 diabetes overall (p > 0.001), the SNP most associated with AAD, rs72975913, was associated with susceptibility to type 1 diabetes in those individuals diagnosed at less than 5 years old (p = 2.3 × 10^−9).</p> <h4>Conclusion/interpretation</h4> <p>PTPRK and its neighbour THEMIS are required for early development of the thymus, which we can assume influences the initiation of autoimmunity. Non-HLA genes may only be detectable as risk factors for the disease in individuals diagnosed under the age 5 years because, after that period of immune development, their role in disease susceptibility has become redundant.</p> |
| spellingShingle | Inshaw, J Walker, N Wallace, C Bottolo, L Todd, J The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age. |
| title | The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age. |
| title_full | The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age. |
| title_fullStr | The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age. |
| title_full_unstemmed | The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age. |
| title_short | The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age. |
| title_sort | chromosome 6q22 33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age |
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