Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

Carina Törn; Xiang Liu; William Hagopian; Åke Lernmark; Olli Simell; Marian Rewers; Anette G. Ziegler; Desmond Schatz; Beena Akolkar; Suna Onengut-Gumuscu; Wei Min Chen; Jorma Toppari; Juha Mykkänen; Jorma Ilonen; Stephen S. Rich; Jin-Xiong She; Ashok Kumar Sharma; Andrea Steck; Jeffrey Krischer

doi:10.1038/srep27887

Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

Carina Törn, Xiang Liu, William Hagopian, Åke Lernmark, Olli Simell, Marian Rewers, Anette G. Ziegler, Desmond Schatz, Beena Akolkar, Suna Onengut-Gumuscu, Wei Min Chen, Jorma Toppari, Juha Mykkänen, Jorma Ilonen, Stephen S. Rich, Jin-Xiong She, Ashok Kumar Sharma, Andrea Steck, Jeffrey Krischer

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Abstract

A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.

Original language	English (US)
Article number	27887
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep27887
State	Published - Jun 16 2016

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Törn, C., Liu, X., Hagopian, W., Lernmark, Å., Simell, O., Rewers, M., Ziegler, A. G., Schatz, D., Akolkar, B., Onengut-Gumuscu, S., Chen, W. M., Toppari, J., Mykkänen, J., Ilonen, J., Rich, S. S., She, J.-X., Sharma, A. K., Steck, A., & Krischer, J. (2016). Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study. Scientific reports, 6, Article 27887. https://doi.org/10.1038/srep27887

Törn, C, Liu, X, Hagopian, W, Lernmark, Å, Simell, O, Rewers, M, Ziegler, AG, Schatz, D, Akolkar, B, Onengut-Gumuscu, S, Chen, WM, Toppari, J, Mykkänen, J, Ilonen, J, Rich, SS, She, J-X, Sharma, AK, Steck, A & Krischer, J 2016, 'Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study', Scientific reports, vol. 6, 27887. https://doi.org/10.1038/srep27887

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title = "Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study",

abstract = "A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.",

author = "Carina T{\"o}rn and Xiang Liu and William Hagopian and {\AA}ke Lernmark and Olli Simell and Marian Rewers and Ziegler, {Anette G.} and Desmond Schatz and Beena Akolkar and Suna Onengut-Gumuscu and Chen, {Wei Min} and Jorma Toppari and Juha Mykk{\"a}nen and Jorma Ilonen and Rich, {Stephen S.} and Jin-Xiong She and Sharma, {Ashok Kumar} and Andrea Steck and Jeffrey Krischer",

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doi = "10.1038/srep27887",

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T1 - Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

AU - Törn, Carina

AU - Liu, Xiang

AU - Hagopian, William

AU - Lernmark, Åke

AU - Simell, Olli

AU - Rewers, Marian

AU - Ziegler, Anette G.

AU - Schatz, Desmond

AU - Akolkar, Beena

AU - Onengut-Gumuscu, Suna

AU - Chen, Wei Min

AU - Toppari, Jorma

AU - Mykkänen, Juha

AU - Ilonen, Jorma

AU - Rich, Stephen S.

AU - She, Jin-Xiong

AU - Sharma, Ashok Kumar

AU - Steck, Andrea

AU - Krischer, Jeffrey

PY - 2016/6/16

Y1 - 2016/6/16

N2 - A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.

AB - A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.

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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

Abstract

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