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.

Groves, C; Zeggini, E; Minton, J; Frayling, T; Weedon, M; Rayner, N; Hitman, G; Walker, M; Wiltshire, S; Hattersley, A; McCarthy, M

Journal article

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.

Abstract:: 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.

Publication status:: Published

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APA Style

Groves, C., Zeggini, E., Minton, J., Frayling, T., Weedon, M., Rayner, N., Hitman, G., Walker, M., Wiltshire, S., Hattersley, A., & McCarthy, M. (2006). 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. Diabetes, 55(9), 2640–2644.

MLA Style

Groves, C., et al. “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.” Diabetes, vol. 55, no. 9, 2006, pp. 2640–44.

Chicago Style

Groves, C, E Zeggini, J Minton, T Frayling, M Weedon, N Rayner, G Hitman, et al. 2006. “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.” Diabetes 55 (9): 2640–44.
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