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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 orcid , 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
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
LU publication?
yes
id
8a2b94b4-8588-4de0-991e-8049a7aca0b5 (old id 1136261)
date added to LUP
2016-04-04 12:21:02
date last changed
2022-03-23 18:58:27
@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}},
  doi          = {{10.1086/507876}},
  volume       = {{79}},
  year         = {{2006}},
}