Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk.
Recent data suggest that common variation in the transcription factor 7-like 2 (TCF7L2) gene is associated with type 2 diabetes. Evaluation of such associations in independent samples provides necessary replication and a robust assessment of effect size. Using four TCF7L2 single nucleotide polymorph...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1797066843953823744 |
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| author | Groves, C Zeggini, E Minton, J Frayling, T Weedon, M Rayner, N Hitman, G Walker, M Wiltshire, S Hattersley, A McCarthy, M |
| author_facet | Groves, C Zeggini, E Minton, J Frayling, T Weedon, M Rayner, N Hitman, G Walker, M Wiltshire, S Hattersley, A McCarthy, M |
| author_sort | Groves, C |
| collection | OXFORD |
| description | Recent data suggest that common variation in the transcription factor 7-like 2 (TCF7L2) gene is associated with type 2 diabetes. Evaluation of such associations in independent samples provides necessary replication and a robust assessment of effect size. Using four TCF7L2 single nucleotide polymorphisms (SNPs; including the two most associated in the previous study), we conducted a case-control study in 2,158 type 2 diabetic subjects and 2,574 control subjects and a family-based association analysis in 388 parent-offspring trios all from the U.K. All SNPs showed powerful associations with diabetes in the case-control analysis, with strongest effects at rs7903146 (allele-wise relative risk 1.36 [95% CI 1.24-1.48], P = 1.3 x 10(-11)). Data were consistent with a multiplicative model. The family-based analyses provided independent evidence for association at all loci (e.g., rs4506565, 62% transmission, P = 7 x 10(-5)) with no parent-of-origin effects. The frequency of diabetes-associated TCF7L2 genotypes was greater in cases ascertained for positive family history and early onset (rs4606565, P = 0.02); the population-attributable risk, estimated from the least-selected cases, is approximately 16%. The overall evidence for association for these variants (P = 4.4 x 10(-14) combining case-control and family-based analyses for rs4506565) exceeds genome-wide significance criteria and clearly establishes TCF7L2 as a type 2 diabetes susceptibility gene of substantial importance. |
| first_indexed | 2024-03-06T21:47:49Z |
| format | Journal article |
| id | oxford-uuid:4a34ccd2-8eff-4814-a4b3-844618a531be |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:47:49Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:4a34ccd2-8eff-4814-a4b3-844618a531be2022-03-26T15:36:14ZAssociation analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4a34ccd2-8eff-4814-a4b3-844618a531beEnglishSymplectic Elements at Oxford2006Groves, CZeggini, EMinton, JFrayling, TWeedon, MRayner, NHitman, GWalker, MWiltshire, SHattersley, AMcCarthy, MRecent data suggest that common variation in the transcription factor 7-like 2 (TCF7L2) gene is associated with type 2 diabetes. Evaluation of such associations in independent samples provides necessary replication and a robust assessment of effect size. Using four TCF7L2 single nucleotide polymorphisms (SNPs; including the two most associated in the previous study), we conducted a case-control study in 2,158 type 2 diabetic subjects and 2,574 control subjects and a family-based association analysis in 388 parent-offspring trios all from the U.K. All SNPs showed powerful associations with diabetes in the case-control analysis, with strongest effects at rs7903146 (allele-wise relative risk 1.36 [95% CI 1.24-1.48], P = 1.3 x 10(-11)). Data were consistent with a multiplicative model. The family-based analyses provided independent evidence for association at all loci (e.g., rs4506565, 62% transmission, P = 7 x 10(-5)) with no parent-of-origin effects. The frequency of diabetes-associated TCF7L2 genotypes was greater in cases ascertained for positive family history and early onset (rs4606565, P = 0.02); the population-attributable risk, estimated from the least-selected cases, is approximately 16%. The overall evidence for association for these variants (P = 4.4 x 10(-14) combining case-control and family-based analyses for rs4506565) exceeds genome-wide significance criteria and clearly establishes TCF7L2 as a type 2 diabetes susceptibility gene of substantial importance. |
| spellingShingle | Groves, C Zeggini, E Minton, J Frayling, T Weedon, M Rayner, N Hitman, G Walker, M Wiltshire, S Hattersley, A McCarthy, M Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. |
| title | Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. |
| title_full | Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. |
| title_fullStr | Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. |
| title_full_unstemmed | Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. |
| title_short | Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. |
| title_sort | association analysis of 6 736 u k subjects provides replication and confirms tcf7l2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk |
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