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 Agardh; Carin 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

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 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

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Artikelnummer	27887
Tidskrift	Scientific Reports
Volym	6
DOI	https://doi.org/10.1038/srep27887
Status	Published - 2016 juni 16

Ämnesklassifikation (UKÄ)

Medicinsk genetik och genomik (Här ingår: Genterapi)
Endokrinologi och diabetes

FN:s Globala mål

Denna forskningsoutput relaterar till följande Globala mål

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10.1038/srep27887

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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., Steck, A., Krischer, J., ... Åberg, S. (2016). Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study. Scientific Reports, 6, Artikel 27887. https://doi.org/10.1038/srep27887

@article{a6bd2edaf6244dc4b346a05436236e9f,

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 She, {Jin Xiong} and Ashok Sharma and Andrea Steck and Jeffrey Krischer and Daniel Agardh and {Andr{\'e}n Aronsson}, Carin and Maria Ask and Rasmus Bennet and Jenny Bremer and Ulla-Marie Carlsson and Corrado Cilio and Helena Larsson and Emelie Ericson-Hallstr{\"o}m and Lina Fransson and Thomas Gard and Joanna Gerardsson and Monica Hansen and Gertie Hansson and Cecilia Harmby and Suzanne Hyberg-Karlsson and Fredrik Johansen and Berglind Jonsdottir and {Lenrick Forss}, Sigrid and Markus Lundgren and Maria Markan and Melin, {Marie Jessica} and Zeliha Mestan and {M{\aa}nsson Martinez}, Maria and Kobra Rahmati and Anita Ramelius and Anna Rosenquist and Falastin Salami and Sara Sibthorpe and Birgitta Sj{\"o}berg and Ulrica Swartling and Amboh, {Evelyn Tekum} and Anne Wallin and {\AA}sa Wimar and Sofie {\AA}berg",

year = "2016",

month = jun,

day = "16",

doi = "10.1038/srep27887",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

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, JX, Sharma, A, Steck, A, Krischer, J, Agardh, D , Andrén Aronsson, C, Ask, M, Bennet, R, Bremer, J, Carlsson, U-M, Cilio, C , Larsson, H , Ericson-Hallström, E, Fransson, L, Gard, T, Gerardsson, J, Hansen, M, Hansson, G, Harmby, C, Hyberg-Karlsson, S, Johansen, F, Jonsdottir, B, Lenrick Forss, S, Lundgren, M, Markan, M, Melin, MJ, Mestan, Z, Månsson Martinez, M, Rahmati, K, Ramelius, A, Rosenquist, A, Salami, F, Sibthorpe, S, Sjöberg, B, Swartling, U, Amboh, ET, Wallin, A, Wimar, Å & Åberg, S 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

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 -

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

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