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Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families

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Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families. / TEDDY Study Group; Hippich, Markus; Beyerlein, Andreas; Hagopian, William A; Krischer, Jeffrey P; Vehik, Kendra; Knoop, Jan; Winker, Christiane; Toppari, Jorma; Lernmark, Åke; Rewers, Marian J; Steck, Andrea K; She, Jin-Xiong; Akolkar, Beena; Robertson, Catherine C; Onengut-Gumuscu, Suna; Rich, Stephen S; Bonifacio, Ezio; Ziegler, Anette-G.

In: Diabetes, Vol. 68, No. 4, 01.04.2019, p. 847-857.

Research output: Contribution to journalArticle

Harvard

TEDDY Study Group, Hippich, M, Beyerlein, A, Hagopian, WA, Krischer, JP, Vehik, K, Knoop, J, Winker, C, Toppari, J, Lernmark, Å, Rewers, MJ, Steck, AK, She, J-X, Akolkar, B, Robertson, CC, Onengut-Gumuscu, S, Rich, SS, Bonifacio, E & Ziegler, A-G 2019, 'Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families', Diabetes, vol. 68, no. 4, pp. 847-857. https://doi.org/10.2337/db18-0882

APA

TEDDY Study Group, Hippich, M., Beyerlein, A., Hagopian, W. A., Krischer, J. P., Vehik, K., ... Ziegler, A-G. (2019). Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families. Diabetes, 68(4), 847-857. https://doi.org/10.2337/db18-0882

Vancouver

TEDDY Study Group, Hippich M, Beyerlein A, Hagopian WA, Krischer JP, Vehik K et al. Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families. Diabetes. 2019 Apr 1;68(4):847-857. https://doi.org/10.2337/db18-0882

Author

TEDDY Study Group ; Hippich, Markus ; Beyerlein, Andreas ; Hagopian, William A ; Krischer, Jeffrey P ; Vehik, Kendra ; Knoop, Jan ; Winker, Christiane ; Toppari, Jorma ; Lernmark, Åke ; Rewers, Marian J ; Steck, Andrea K ; She, Jin-Xiong ; Akolkar, Beena ; Robertson, Catherine C ; Onengut-Gumuscu, Suna ; Rich, Stephen S ; Bonifacio, Ezio ; Ziegler, Anette-G. / Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families. In: Diabetes. 2019 ; Vol. 68, No. 4. pp. 847-857.

Bibtex

@article{0dab6070be93449894b5f0dfc897243a,
title = "Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families",
abstract = "The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes (n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes-associated genes and a novel risk gene, BTNL2, was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95{\%} CI 1.6-3.02]) and for diabetes (HR 2.92 [95{\%} CI 2.05-4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3{\%} vs .12.7{\%}) and diabetes (4.8{\%} vs. 4.1{\%}) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.",
author = "{TEDDY Study Group} and Markus Hippich and Andreas Beyerlein and Hagopian, {William A} and Krischer, {Jeffrey P} and Kendra Vehik and Jan Knoop and Christiane Winker and Jorma Toppari and {\AA}ke Lernmark and Rewers, {Marian J} and Steck, {Andrea K} and Jin-Xiong She and Beena Akolkar and Robertson, {Catherine C} and Suna Onengut-Gumuscu and Rich, {Stephen S} and Ezio Bonifacio and Anette-G Ziegler and Polly Bingley",
note = "{\circledC} 2019 by the American Diabetes Association.",
year = "2019",
month = "4",
day = "1",
doi = "10.2337/db18-0882",
language = "English",
volume = "68",
pages = "847--857",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "4",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families

AU - TEDDY Study Group

AU - Hippich, Markus

AU - Beyerlein, Andreas

AU - Hagopian, William A

AU - Krischer, Jeffrey P

AU - Vehik, Kendra

AU - Knoop, Jan

AU - Winker, Christiane

AU - Toppari, Jorma

AU - Lernmark, Åke

AU - Rewers, Marian J

AU - Steck, Andrea K

AU - She, Jin-Xiong

AU - Akolkar, Beena

AU - Robertson, Catherine C

AU - Onengut-Gumuscu, Suna

AU - Rich, Stephen S

AU - Bonifacio, Ezio

AU - Ziegler, Anette-G

AU - Bingley, Polly

N1 - © 2019 by the American Diabetes Association.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes (n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes-associated genes and a novel risk gene, BTNL2, was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95% CI 1.6-3.02]) and for diabetes (HR 2.92 [95% CI 2.05-4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3% vs .12.7%) and diabetes (4.8% vs. 4.1%) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.

AB - The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes (n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes-associated genes and a novel risk gene, BTNL2, was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95% CI 1.6-3.02]) and for diabetes (HR 2.92 [95% CI 2.05-4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3% vs .12.7%) and diabetes (4.8% vs. 4.1%) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.

U2 - 10.2337/db18-0882

DO - 10.2337/db18-0882

M3 - Article

VL - 68

SP - 847

EP - 857

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -