AIM: The aim of this study was to test chromosomes carrying the same DRB1-DQA1-DQB1 haplotype for single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) that might mark subgroups of the haplotype with different risks for type 1 diabetes (T1D). METHODS: Chromosomes from T1D children, their parents and non-diabetic siblings in families of the Type 1 Diabetes Genetics Consortium (T1DGC) were analysed by two haplotype-based methods: (i) logistic regression analysis restricted to phased chromosomes carrying the same DRB1-DQA1-DQB1 haplotype but differentiated by the two alleles at MHC SNPs, which were individually tested for association with T1D and (ii) homozygous parent transmission disequilibrium test (TDT) for biased transmission of a SNP allele to diabetic children from parents who are heterozygous at the SNP but homozygous for the specific DRB1-DQA1-DQB1 haplotype being evaluated. RESULTS: A number of SNPs gave nominally significant (p < 0.05) evidence of marking two subsets of the 301-501-201 haplotype that might differ with respect to their diabetogenic potency. However, none of the SNPs achieved experiment-wide significance and hence may be false-positive associations. CONCLUSIONS: We discuss limitations and possible deficiencies of our study suggesting further work that might yield more robust SNP associations marking two subgroups of a DRB1-DQA1-DQB1 haplotype with different T1D risks.
AIM: The aim of this study was to test chromosomes carrying the same DRB1-DQA1-DQB1 haplotype for single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) that might mark subgroups of the haplotype with different risks for type 1 diabetes (T1D). METHODS: Chromosomes from T1D children, their parents and non-diabetic siblings in families of the Type 1 Diabetes Genetics Consortium (T1DGC) were analysed by two haplotype-based methods: (i) logistic regression analysis restricted to phased chromosomes carrying the same DRB1-DQA1-DQB1 haplotype but differentiated by the two alleles at MHC SNPs, which were individually tested for association with T1D and (ii) homozygous parent transmission disequilibrium test (TDT) for biased transmission of a SNP allele to diabeticchildren from parents who are heterozygous at the SNP but homozygous for the specific DRB1-DQA1-DQB1 haplotype being evaluated. RESULTS: A number of SNPs gave nominally significant (p < 0.05) evidence of marking two subsets of the 301-501-201 haplotype that might differ with respect to their diabetogenic potency. However, none of the SNPs achieved experiment-wide significance and hence may be false-positive associations. CONCLUSIONS: We discuss limitations and possible deficiencies of our study suggesting further work that might yield more robust SNP associations marking two subgroups of a DRB1-DQA1-DQB1 haplotype with different T1D risks.
Authors: R Lampis; L Morelli; M Congia; M D Macis; A Mulargia; M Loddo; S De Virgiliis; M G Marrosu; J A Todd; F Cucca Journal: Hum Mol Genet Date: 2000-12-12 Impact factor: 6.150
Authors: Marcos M Miretti; Emily C Walsh; Xiayi Ke; Marcos Delgado; Mark Griffiths; Sarah Hunt; Jonathan Morrison; Pamela Whittaker; Eric S Lander; Lon R Cardon; David R Bentley; John D Rioux; Stephan Beck; Panos Deloukas Journal: Am J Hum Genet Date: 2005-03-01 Impact factor: 11.025
Authors: B A Lie; J A Todd; F Pociot; J Nerup; H E Akselsen; G Joner; K Dahl-Jørgensen; K S Rønningen; E Thorsby; D E Undlien Journal: Am J Hum Genet Date: 1999-03 Impact factor: 11.025
Authors: G Thomson; A M Valdes; J A Noble; I Kockum; M N Grote; J Najman; H A Erlich; F Cucca; A Pugliese; A Steenkiste; J S Dorman; S Caillat-Zucman; R Hermann; J Ilonen; A P Lambert; P J Bingley; K M Gillespie; A Lernmark; C B Sanjeevi; K S Rønningen; D E Undlien; E Thorsby; A Petrone; R Buzzetti; B P C Koeleman; B O Roep; G Saruhan-Direskeneli; F A Uyar; H Günoz; C Gorodezky; C Alaez; B O Boehm; W Mlynarski; H Ikegami; M Berrino; M E Fasano; E Dametto; S Israel; C Brautbar; A Santiago-Cortes; T Frazer de Llado; J-X She; T L Bugawan; J I Rotter; L Raffel; A Zeidler; F Leyva-Cobian; B R Hawkins; S H Chan; L Castano; F Pociot; J Nerup Journal: Tissue Antigens Date: 2007-08
Authors: Paul I W de Bakker; Gil McVean; Pardis C Sabeti; Marcos M Miretti; Todd Green; Jonathan Marchini; Xiayi Ke; Alienke J Monsuur; Pamela Whittaker; Marcos Delgado; Jonathan Morrison; Angela Richardson; Emily C Walsh; Xiaojiang Gao; Luana Galver; John Hart; David A Hafler; Margaret Pericak-Vance; John A Todd; Mark J Daly; John Trowsdale; Cisca Wijmenga; Tim J Vyse; Stephan Beck; Sarah Shaw Murray; Mary Carrington; Simon Gregory; Panos Deloukas; John D Rioux Journal: Nat Genet Date: 2006-09-24 Impact factor: 38.330
Authors: Mary Helen Black; Jean M Lawrence; Catherine Pihoker; Lawrence M Dolan; Andrea Anderson; Beatriz Rodriguez; Santica M Marcovina; Elizabeth J Mayer-Davis; Giuseppina Imperatore; Dana Dabelea Journal: Pediatr Diabetes Date: 2012-08-23 Impact factor: 4.866