The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes

Jason D. Cooper, Deborah J. Smyth, Rebecca Bailey, Felicity Payne, Kate Downes, Lisa M. Godfrey, Jennifer Masters, Lauren R. Zeitels, Adrian Vella, Neil M. Walker, John A. Todd

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Abstract

Background: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes. Methods: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region. Results: We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 × 10-4). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region. Conclusion: We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.

Original languageEnglish (US)
Article number71
JournalBMC Medical Genetics
Volume8
DOIs
StatePublished - Nov 28 2007

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Type 1 Diabetes Mellitus
Interleukin-6
Genes
Genome-Wide Association Study
Immune System Diseases
Single Nucleotide Polymorphism
Sample Size

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

Cite this

Cooper, J. D., Smyth, D. J., Bailey, R., Payne, F., Downes, K., Godfrey, L. M., ... Todd, J. A. (2007). The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes. BMC Medical Genetics, 8, [71]. https://doi.org/10.1186/1471-2350-8-71

The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes. / Cooper, Jason D.; Smyth, Deborah J.; Bailey, Rebecca; Payne, Felicity; Downes, Kate; Godfrey, Lisa M.; Masters, Jennifer; Zeitels, Lauren R.; Vella, Adrian; Walker, Neil M.; Todd, John A.

In: BMC Medical Genetics, Vol. 8, 71, 28.11.2007.

Research output: Contribution to journalArticle

Cooper, JD, Smyth, DJ, Bailey, R, Payne, F, Downes, K, Godfrey, LM, Masters, J, Zeitels, LR, Vella, A, Walker, NM & Todd, JA 2007, 'The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes', BMC Medical Genetics, vol. 8, 71. https://doi.org/10.1186/1471-2350-8-71
Cooper, Jason D. ; Smyth, Deborah J. ; Bailey, Rebecca ; Payne, Felicity ; Downes, Kate ; Godfrey, Lisa M. ; Masters, Jennifer ; Zeitels, Lauren R. ; Vella, Adrian ; Walker, Neil M. ; Todd, John A. / The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes. In: BMC Medical Genetics. 2007 ; Vol. 8.
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abstract = "Background: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes. Methods: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region. Results: We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 × 10-4). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region. Conclusion: We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.",
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AU - Cooper, Jason D.

AU - Smyth, Deborah J.

AU - Bailey, Rebecca

AU - Payne, Felicity

AU - Downes, Kate

AU - Godfrey, Lisa M.

AU - Masters, Jennifer

AU - Zeitels, Lauren R.

AU - Vella, Adrian

AU - Walker, Neil M.

AU - Todd, John A.

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N2 - Background: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes. Methods: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region. Results: We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 × 10-4). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region. Conclusion: We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.

AB - Background: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes. Methods: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region. Results: We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 × 10-4). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region. Conclusion: We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.

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