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

J C Roach, K Deutsch, S Li, A F Siegel, L M Bekris, D C Einhaus, M Janer, C M Sheridan, G Glusman, Åke Lernmark, L Hood, Diabetes Incidence in Sweden Study Group., Swedish Childhood Diabetes Study Group

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46 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)614-627
JournalAmerican Journal of Human Genetics
Volume79
Issue number4
DOIs
Publication statusPublished - 2006

Subject classification (UKÄ)

  • Endocrinology and Diabetes

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