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Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden.

Roach, J C; Deutsch, K; Li, S; Siegel, A F; Bekris, L M; Einhaus, D C; Janer, M; Sheridan, C M; Glusman, G and Lernmark, Åke LU , et al. (2006) In American Journal of Human Genetics 79(4). p.614-627
Abstract
We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the MHC, initially in a survey of 363 Swedish T1D cases and controls. We confirmed prior studies showing association with T1D in the MHC, most significantly near HLA-DR/DQ. In the region centromeric to the MHC, we identified a peak of association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3; formerly IP3R3). The most significant single SNP in this region was at the center of the ITPR3 peak of association (P=1.7×10−4 for the survey study). For validation, we typed an additional 761 Swedish individuals. The... (More)
We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the MHC, initially in a survey of 363 Swedish T1D cases and controls. We confirmed prior studies showing association with T1D in the MHC, most significantly near HLA-DR/DQ. In the region centromeric to the MHC, we identified a peak of association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3; formerly IP3R3). The most significant single SNP in this region was at the center of the ITPR3 peak of association (P=1.7×10−4 for the survey study). For validation, we typed an additional 761 Swedish individuals. The P value for association computed from all 1,124 individuals was 1.30×10−6 (recessive odds ratio 2.5; 95% confidence interval [CI] 1.7–3.9). The estimated population-attributable risk of 21.6% (95% CI 10.0%–31.0%) suggests that variation within ITPR3 reflects an important contribution to T1D in Sweden. Two-locus regression analysis supports an influence of ITPR3 variation on T1D that is distinct from that of any MHC class II gene. (Less)
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American Journal of Human Genetics
volume
79
issue
4
pages
614 - 627
publisher
Cell Press
external identifiers
  • scopus:33749010061
ISSN
0002-9297
DOI
10.1086/507876
language
English
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yes
id
8a2b94b4-8588-4de0-991e-8049a7aca0b5 (old id 1136261)
date added to LUP
2008-06-16 12:53:58
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2017-02-26 04:33:12
@article{8a2b94b4-8588-4de0-991e-8049a7aca0b5,
  abstract     = {We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the MHC, initially in a survey of 363 Swedish T1D cases and controls. We confirmed prior studies showing association with T1D in the MHC, most significantly near HLA-DR/DQ. In the region centromeric to the MHC, we identified a peak of association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3; formerly IP3R3). The most significant single SNP in this region was at the center of the ITPR3 peak of association (P=1.7×10−4 for the survey study). For validation, we typed an additional 761 Swedish individuals. The P value for association computed from all 1,124 individuals was 1.30×10−6 (recessive odds ratio 2.5; 95% confidence interval [CI] 1.7–3.9). The estimated population-attributable risk of 21.6% (95% CI 10.0%–31.0%) suggests that variation within ITPR3 reflects an important contribution to T1D in Sweden. Two-locus regression analysis supports an influence of ITPR3 variation on T1D that is distinct from that of any MHC class II gene.},
  author       = {Roach, J C and Deutsch, K and Li, S and Siegel, A F and Bekris, L M and Einhaus, D C and Janer, M and Sheridan, C M and Glusman, G and Lernmark, Åke and Hood, L and Study Group., Diabetes Incidence in Sweden and Study Group, Swedish Childhood Diabetes},
  issn         = {0002-9297},
  language     = {eng},
  number       = {4},
  pages        = {614--627},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden.},
  url          = {http://dx.doi.org/10.1086/507876},
  volume       = {79},
  year         = {2006},
}