IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells

Siyang Liu, Hongjie Wang, Yulan Jin, Robert Podolsky, M. V.Prasad Linga Reddy, Jennifer Pedersen, Bruce Bode, John Reed, Dennis Steed, Steve Anderson, Ping Yang, Andy Muir, Leigh Steed, Diane Hopkins, Yihua Huang, Sharad B Purohit, Cong Yi Wang, Andrea K. Steck, Annalisa Montemari, George EisenbarthMarian Rewers, Jin-Xiong She

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Abstract

Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5′ region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 × 10-8 and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.

Original languageEnglish (US)
Pages (from-to)358-365
Number of pages8
JournalHuman Molecular Genetics
Volume18
Issue number2
DOIs
StatePublished - Jan 1 2009

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Type 1 Diabetes Mellitus
Single Nucleotide Polymorphism
Blood Cells
Gene Expression
Chromosomes, Human, Pair 5
Linkage Disequilibrium
Odds Ratio
Genotype
Genes
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 3
Genome-Wide Association Study
Chromosomes
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells. / Liu, Siyang; Wang, Hongjie; Jin, Yulan; Podolsky, Robert; Reddy, M. V.Prasad Linga; Pedersen, Jennifer; Bode, Bruce; Reed, John; Steed, Dennis; Anderson, Steve; Yang, Ping; Muir, Andy; Steed, Leigh; Hopkins, Diane; Huang, Yihua; Purohit, Sharad B; Wang, Cong Yi; Steck, Andrea K.; Montemari, Annalisa; Eisenbarth, George; Rewers, Marian; She, Jin-Xiong.

In: Human Molecular Genetics, Vol. 18, No. 2, 01.01.2009, p. 358-365.

Research output: Contribution to journalArticle

Liu, S, Wang, H, Jin, Y, Podolsky, R, Reddy, MVPL, Pedersen, J, Bode, B, Reed, J, Steed, D, Anderson, S, Yang, P, Muir, A, Steed, L, Hopkins, D, Huang, Y, Purohit, SB, Wang, CY, Steck, AK, Montemari, A, Eisenbarth, G, Rewers, M & She, J-X 2009, 'IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells', Human Molecular Genetics, vol. 18, no. 2, pp. 358-365. https://doi.org/10.1093/hmg/ddn342
Liu, Siyang ; Wang, Hongjie ; Jin, Yulan ; Podolsky, Robert ; Reddy, M. V.Prasad Linga ; Pedersen, Jennifer ; Bode, Bruce ; Reed, John ; Steed, Dennis ; Anderson, Steve ; Yang, Ping ; Muir, Andy ; Steed, Leigh ; Hopkins, Diane ; Huang, Yihua ; Purohit, Sharad B ; Wang, Cong Yi ; Steck, Andrea K. ; Montemari, Annalisa ; Eisenbarth, George ; Rewers, Marian ; She, Jin-Xiong. / IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 2. pp. 358-365.
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abstract = "Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5′ region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 × 10-8 and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.",
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T1 - IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells

AU - Liu, Siyang

AU - Wang, Hongjie

AU - Jin, Yulan

AU - Podolsky, Robert

AU - Reddy, M. V.Prasad Linga

AU - Pedersen, Jennifer

AU - Bode, Bruce

AU - Reed, John

AU - Steed, Dennis

AU - Anderson, Steve

AU - Yang, Ping

AU - Muir, Andy

AU - Steed, Leigh

AU - Hopkins, Diane

AU - Huang, Yihua

AU - Purohit, Sharad B

AU - Wang, Cong Yi

AU - Steck, Andrea K.

AU - Montemari, Annalisa

AU - Eisenbarth, George

AU - Rewers, Marian

AU - She, Jin-Xiong

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5′ region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 × 10-8 and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.

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