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

Smyth, Deborah J.; Cooper, Jason D.; Bailey, Rebecca; Field, Sarah; Burren, Oliver S.; Smink, Luc J.; Guja, Cristian; Ionescu-Tîrgovişte, C; Widmer, Barry; Dunger, David B.; Savage, David A.; Walker, Neil M.; Clayton, David; Todd, John A.

doi:10.1038/ng1800

Cited by 613 publications

(500 citation statements)

References 15 publications

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“…We have studied one of these new regions on chromosome 5p13 [8,9]. The same SNP from CAPSL (rs1445898) that was already described showed a trend towards association in our Spanish and Dutch cohorts, supporting the role of this locus in type 1 diabetes risk (Tables 1 and 2).…”

Section: Discussionsupporting

confidence: 78%

“…Smyth et al [8] found an association between two new single nucleotide polymorphisms (SNPs) and type 1 diabetes in a genome-wide scan study of non-synonymous SNPs. The first new SNP was rs1445898 from the CAPSL gene (calcyphosine-like; also known as Q8WWF8) on chromosome 5p13; the second was rs19907060 from the interferon induced with helicase C domain 1 (IFIH1) gene on chromosome 2q24.3.…”

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confidence: 99%

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Study of the association between the CAPSL-IL7R locus and type 1 diabetes

et al. 2008

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Aims/hypothesis In the past few years, several genes outside the MHC region have been described as new susceptibility genetic factors to type 1 diabetes. An association between CAPSL-rs1445898 and type 1 diabetes was reported in a large white population and corroborated in a genome-wide analysis, which also found an association with IL7R, which is located adjacent to CAPSL. The aim of this study was to replicate the aforementioned associations in independent cohorts. Methods We analysed two CAPSL (rs1010601 and rs1445898) and three IL7R (rs6897932, rs987106 and rs3194051) polymorphisms. All these single nucleotide polymorphisms (SNPs) were genotyped using TaqMan minor groove binder chemistry in 301 unrelated Spanish type 1 diabetes patients and 646 healthy controls. Additionally, the associated CAPSL SNP rs1445898 was Conclusions/interpretation In summary, we describe an independent replication of the association between the CAPSL-IL7R locus and type 1 diabetes, especially for early-onset type 1 diabetes patients.

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Section: Discussionsupporting

confidence: 78%

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confidence: 99%

Study of the association between the CAPSL-IL7R locus and type 1 diabetes

et al. 2008

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“…18 To date, no studies have been published examining genotypic differences in IL7Ra between sarcoidosis patients and controls. We genotyped six common single-nucleotide polymorphisms (SNPs) spanning IL7R, including the 5 0 promoter, a SNP in intron 5, a nonsynonymous SNP in exon 8 and three haplotypetagging SNPs.…”

Section: Introductionmentioning

confidence: 99%

Variation in IL7R predisposes to sarcoid inflammation

et al. 2009

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Sarcoidosis is a chronic granulomatous disorder characterized by a massive influx of Th1 lymphocytes. Both naive and memory T cells express high levels of interleukin 7 receptor-a (IL7Ra), encoded by the IL7R gene. The purpose of this study was to investigate the role of the IL7R gene region in susceptibility to sarcoidosis. Six common single-nucleotide polymorphisms (SNPs) spanning IL7R were genotyped and analyzed in 475 sarcoidosis patients and 465 healthy controls. Replication of one significant associated SNP was carried out in 206 independent sarcoidosis patients, 127 controls and 126 patients with Lö fgren's disease. The rs10213865 SNP was associated with sarcoidosis (P ¼ 0.008), and in silico analysis showed a complete linkage (r 2 ¼ 1, D 0 ¼ 1) with a functional nonsynonymous coding SNP in exon 6 (rs6897932, T244I). Combined analysis of 663 individuals with sarcoidosis and 586 controls (homozygous carriers of risk allele, P ¼ 5 Â 10 À4 , odds ratio ¼ 1.49 (1.19-1.86)) provided strong statistical support for a genuine association of IL7R with the risk of sarcoidosis. In addition, we report the same trend between variation in the IL7R gene and patients with Lö fgren's disease, suggesting that variation in IL7R may confer general risk for developing granulomatous lung disease.

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“…The most important genetic factors for determining the risk of developing T1DM reside in the HLA class II loci but also, according to recent findings, in the HLA-B and HLA-A class I genes [2]. Several other gene regions have also been identified: a region 5′ to the INS gene, CTLA4, PTPN22, IL2RA, and the IFIH1 region [3,4]. A recent T1DM genome-wide association study identified another four regions at 12q24, 12q13, 16p13, and 18p11 [5].…”

Section: Introductionmentioning

confidence: 99%