Aims/hypothesis: We used recently confirmed type 2 diabetes gene regions to investigate the genetic relationship between type 1 and type 2 diabetes, in an average of 7,606 type 1 diabetic individuals and 8,218 controls, providing >80% power to detect effects as small as an OR of 1.11 at a false-positive rate of 0.003. Methods: The single nucleotide polymorphisms (SNPs) with the most convincing evidence of association in 12 type 2 diabetes-associated gene regions, PPARG, CDKAL1, HNF1B, WFS1, SLC30A8, CDKN2A-CDKN2B, IGF2BP2, KCNJ11, TCF7L2, FTO, HHEX-IDE and THADA, were analysed in type 1 diabetes cases and controls. PPARG and HHEX-IDE were additionally tested for association in 3,851 type 1 diabetes families. Tests for interaction with HLA class II genotypes, autoantibody status, sex, and age-at-diagnosis of type 1 diabetes were performed with all 12 gene regions. Results: Only PPARG and HHEX-IDE showed any evidence of association with type 1 diabetes cases and controls (p=0.004 and p=0.003, respectively; p>0.05 for other SNPs). The potential association of PPARG was supported by family analyses (p=0.003; p combined=1.0×10 -4). No SNPs showed evidence of interaction with any covariate (p>0.05). Conclusions/interpretation: We found no convincing genetic link between type 1 and type 2 diabetes. An association of PPARG (rs1801282/Pro12Ala) could be consistent with its known function in inflammation. Hence, our results reinforce evidence suggesting that type 1 diabetes is a disease of the immune system, rather than being due to inherited defects in beta cell function or regeneration or insulin resistance.
CITATION STYLE
Raj, S. M., Howson, J. M. M., Walker, N. M., Cooper, J. D., Smyth, D. J., Field, S. F., … Todd, J. A. (2009). No association of multiple type 2 diabetes loci with type 1 diabetes. Diabetologia, 52(10), 109–116. https://doi.org/10.1007/s00125-009-1391-y
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