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 Sharma, Andrea Steck, Jeffrey Krischer, Daniel AgardhCarin Andrén Aronsson, Maria Ask, Rasmus Bennet, Jenny Bremer, Ulla-Marie Carlsson, Corrado Cilio, Helena Larsson, Emelie Ericson-Hallström, Lina Fransson, Thomas Gard, Joanna Gerardsson, Monica Hansen, Gertie Hansson, Cecilia Harmby, Suzanne Hyberg-Karlsson, Fredrik Johansen, Berglind Jonsdottir, Sigrid Lenrick Forss, Markus Lundgren, Maria Markan, Marie Jessica Melin, Zeliha Mestan, Maria Månsson Martinez, Kobra Rahmati, Anita Ramelius, Anna Rosenquist, Falastin Salami, Sara Sibthorpe, Birgitta Sjöberg, Ulrica Swartling, Evelyn Tekum Amboh, Anne Wallin, Åsa Wimar, Sofie Åberg

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18 Citations (SciVal)


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
Article number27887
JournalScientific Reports
Publication statusPublished - 2016 Jun 16

Subject classification (UKÄ)

  • Medical Genetics
  • Endocrinology and Diabetes


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