TY - JOUR
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
AU - Steck, Andrea
AU - Krischer, Jeffrey
AU - Agardh, Daniel
AU - Andrén Aronsson, Carin
AU - Ask, Maria
AU - Bennet, Rasmus
AU - Bremer, Jenny
AU - Carlsson, Ulla-Marie
AU - Cilio, Corrado
AU - Larsson, Helena
AU - Ericson-Hallström, Emelie
AU - Fransson, Lina
AU - Gard, Thomas
AU - Gerardsson, Joanna
AU - Hansen, Monica
AU - Hansson, Gertie
AU - Harmby, Cecilia
AU - Hyberg-Karlsson, Suzanne
AU - Johansen, Fredrik
AU - Jonsdottir, Berglind
AU - Lenrick Forss, Sigrid
AU - Lundgren, Markus
AU - Markan, Maria
AU - Melin, Marie Jessica
AU - Mestan, Zeliha
AU - Månsson Martinez, Maria
AU - Rahmati, Kobra
AU - Ramelius, Anita
AU - Rosenquist, Anna
AU - Salami, Falastin
AU - Sibthorpe, Sara
AU - Sjöberg, Birgitta
AU - Swartling, Ulrica
AU - Amboh, Evelyn Tekum
AU - Wallin, Anne
AU - Wimar, Åsa
AU - Åberg, Sofie
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.
UR - http://www.scopus.com/inward/record.url?scp=84975091581&partnerID=8YFLogxK
U2 - 10.1038/srep27887
DO - 10.1038/srep27887
M3 - Article
C2 - 27306948
AN - SCOPUS:84975091581
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 27887
ER -