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 languageEnglish (US)
Article number27887
JournalScientific Reports
Volume6
DOIs
StatePublished - Jun 16 2016

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Type 1 Diabetes Mellitus
Autoantibodies
Single Nucleotide Polymorphism
Antigens
Genes
Autoimmunity

ASJC Scopus subject areas

  • General

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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study. / Törn, Carina; Liu, Xiang; Hagopian, William; Lernmark, Åke; Simell, Olli; Rewers, Marian; Ziegler, Anette G.; Schatz, Desmond; Akolkar, Beena; Onengut-Gumuscu, Suna; Chen, Wei Min; Toppari, Jorma; Mykkänen, Juha; Ilonen, Jorma; Rich, Stephen S.; She, Jin-Xiong; Sharma, Ashok Kumar; Steck, Andrea; Krischer, Jeffrey.

In: Scientific Reports, Vol. 6, 27887, 16.06.2016.

Research output: Contribution to journalArticle

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
Törn, Carina ; Liu, Xiang ; Hagopian, William ; Lernmark, Åke ; Simell, Olli ; Rewers, Marian ; Ziegler, Anette G. ; Schatz, Desmond ; Akolkar, Beena ; Onengut-Gumuscu, Suna ; Chen, Wei Min ; Toppari, Jorma ; Mykkänen, Juha ; Ilonen, Jorma ; Rich, Stephen S. ; She, Jin-Xiong ; Sharma, Ashok Kumar ; Steck, Andrea ; Krischer, Jeffrey. / Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study. In: Scientific Reports. 2016 ; Vol. 6.
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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.",
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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

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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.

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