A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region

@article{Smyth2006AGA,
  title={A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region},
  author={Deborah J. Smyth and Jason D Cooper and Rebecca Bailey and Sarah F Field and Oliver S. Burren and Luc J. Smink and Cristian Guja and Constantin Ionescu-Tirgoviste and Barry Widmer and David B. Dunger and David A. Savage and Neil M. Walker and David Clayton and John A. Todd},
  journal={Nature Genetics},
  year={2006},
  volume={38},
  pages={617-619}
}
In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio… 
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The findings indicate that IFIH1 genotypes influence progression from autoimmunity to diabetes development, consistent with the notion that protective genotypes downregulate responses to environmental insults after initiation of autoimmonity.
No association of type 1 diabetes with a functional polymorphism of the LRAP gene.
TLDR
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Rare Variants of IFIH1, a Gene Implicated in Antiviral Responses, Protect Against Type 1 Diabetes
TLDR
This work resequenced exons and splice sites of 10 candidate genes in pools of DNA from 480 patients and 480 controls and tested their disease association in over 30,000 participants to establish the role of IFIH1 and demonstrate that resequencing studies can pinpoint disease-causing genes in genomic regions initially identified by GWASs.
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
TLDR
These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
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References

SHOWING 1-10 OF 16 REFERENCES
Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms.
TLDR
The results illustrate the utility of tag SNPs in a chromosome-regional test of disease association and justify future fine mapping of the causal variant in the region.
Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus.
TLDR
A more general association of the PTPN22 locus with autoimmune disease is indicated, as reported for an association of Trp(620) with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects.
Remapping the insulin gene/IDDM2 locus in type 1 diabetes.
TLDR
Mapping results using robust regression methods show how precisely a variant for a common disease can be mapped, even within a region of strong LD, and specifically that IDDM2 maps to one or more of three common variants in a approximately 2-kb region of chromosome 11p15.
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry.
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21
Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the
A Polymorphic Locus Near the Human Insulin Gene Is Associated with Insulin-dependent Diabetes Melliitus
TLDR
The genotype at this locus of 393 unrelated diabetic and nondiabetic individuals is determined and differences were observed in the genotypie and allelic frequencies between groups of different races.
Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay.
TLDR
The suitability of Molecular Inversion Probe technology with four-color, single array detection, applied to large-scale genotyping of up to 12,000 SNPs per reaction is demonstrated, demonstrating the ability of the technology to suppress cross-reactivity at high multiplex levels.
Population structure, differential bias and genomic control in a large-scale, case-control association study
TLDR
To avoid excluding SNPs and losing valuable information, the genomic control method is extended by applying a variable downweighting to each SNP, which explains part of the significant +11.2% inflation of test statistics the authors observed in an analysis of 6,322 nonsynonymous SNPs.
A correlation between the relative predisposition of MHC class II alleles to type 1 diabetes and the structure of their proteins.
TLDR
The data provide evidence for a joint action of the class II peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance with a main role for P 9 in DQ/IA and for P1 and P4 in DR/IE.
A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes
We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1
...
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