AIMS/HYPOTHESIS: A complex region covering numerous genes in 12q13 was first associated with type 1 diabetes in the Wellcome Trust Case-Control Consortium (WTCCC) study. Two studies performed in a white population have tested the association of polymorphisms within this region with age at onset of the disease, with seemingly contradictory results. We aimed at replicating three of the strongest signals in a group of patients with early and late disease onset. METHODS: Polymorphisms rs773107, rs2292239 and rs10876864 were genotyped in 444 type 1 diabetic Spanish participants (age at onset 0-65 years) and 861 controls. The influence of single nucleotide polymorphisms (SNPs) on age at onset was tested through stratified and continuous analyses. RESULTS: rs773107 and rs2292239 were significantly associated with the disease, while rs10876864 showed a trend towards statistical significance in the whole population analyses. Comparison of early-onset patients to controls was significant for the three polymorphisms (allelic p < 0.006). Late-onset patients and controls did not reveal statistical differences. Analysis of age at onset in both rs773107 and rs2292239 showed differences between genotypes (p ≤ 0.002), alleles (p ≤ 0.013) and homozygotes for the risk genotype (p ≤ 4 × 10(-4)). Polymorphism rs10876864 showed trends towards statistical significance in the allelic frequencies (p = 0.051) and homozygotes for the risk genotype (p = 0.056). Subjects with risk genotypes had a disease onset between 2 and 5 years earlier than carriers of protective alleles. CONCLUSIONS/ INTERPRETATION: We replicate two of the previously studied associations in a Spanish population and find new evidence of the influence of the 12q13 region on age at onset of type 1 diabetes.
AIMS/HYPOTHESIS: A complex region covering numerous genes in 12q13 was first associated with type 1 diabetes in the Wellcome Trust Case-Control Consortium (WTCCC) study. Two studies performed in a white population have tested the association of polymorphisms within this region with age at onset of the disease, with seemingly contradictory results. We aimed at replicating three of the strongest signals in a group of patients with early and late disease onset. METHODS: Polymorphisms rs773107, rs2292239 and rs10876864 were genotyped in 444 type 1 diabetic Spanish participants (age at onset 0-65 years) and 861 controls. The influence of single nucleotide polymorphisms (SNPs) on age at onset was tested through stratified and continuous analyses. RESULTS: rs773107 and rs2292239 were significantly associated with the disease, while rs10876864 showed a trend towards statistical significance in the whole population analyses. Comparison of early-onset patients to controls was significant for the three polymorphisms (allelic p < 0.006). Late-onset patients and controls did not reveal statistical differences. Analysis of age at onset in both rs773107 and rs2292239 showed differences between genotypes (p ≤ 0.002), alleles (p ≤ 0.013) and homozygotes for the risk genotype (p ≤ 4 × 10(-4)). Polymorphism rs10876864 showed trends towards statistical significance in the allelic frequencies (p = 0.051) and homozygotes for the risk genotype (p = 0.056). Subjects with risk genotypes had a disease onset between 2 and 5 years earlier than carriers of protective alleles. CONCLUSIONS/ INTERPRETATION: We replicate two of the previously studied associations in a Spanish population and find new evidence of the influence of the 12q13 region on age at onset of type 1 diabetes.
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Authors: Hongjie Wang; Yulan Jin; M V Prasad Linga Reddy; Robert Podolsky; Siyang Liu; Ping Yang; Bruce Bode; John Chip Reed; R Dennis Steed; Stephen W Anderson; Leigh Steed; Diane Hopkins; Yihua Huang; Jin-Xiong She Journal: PLoS One Date: 2010-07-26 Impact factor: 3.240
Authors: John A Todd; Neil M Walker; Jason D Cooper; Deborah J Smyth; Kate Downes; Vincent Plagnol; Rebecca Bailey; Sergey Nejentsev; Sarah F Field; Felicity Payne; Christopher E Lowe; Jeffrey S Szeszko; Jason P Hafler; Lauren Zeitels; Jennie H M Yang; Adrian Vella; Sarah Nutland; Helen E Stevens; Helen Schuilenburg; Gillian Coleman; Meeta Maisuria; William Meadows; Luc J Smink; Barry Healy; Oliver S Burren; Alex A C Lam; Nigel R Ovington; James Allen; Ellen Adlem; Hin-Tak Leung; Chris Wallace; Joanna M M Howson; Cristian Guja; Constantin Ionescu-Tîrgovişte; Matthew J Simmonds; Joanne M Heward; Stephen C L Gough; David B Dunger; Linda S Wicker; David G Clayton Journal: Nat Genet Date: 2007-06-06 Impact factor: 38.330
Authors: Joanna M M Howson; Jason D Cooper; Deborah J Smyth; Neil M Walker; Helen Stevens; Jin-Xiong She; George S Eisenbarth; Marian Rewers; John A Todd; Beena Akolkar; Patrick Concannon; Henry A Erlich; Cécile Julier; Grant Morahan; Jørn Nerup; Concepcion Nierras; Flemming Pociot; Stephen S Rich Journal: Diabetes Date: 2012-08-13 Impact factor: 9.461