PuSH - Publication Server of Helmholtz Zentrum München: Genetic contribution to the divergence in type 1 diabetes risk between children from the general population and children from affected families.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Hippich, M. ; Beyerlein, A. ; Hagopian, W.A.* ; Krischer, J.P.* ; Vehik, K.* ; Knoop, J. ; Winker, C. ; Toppari, J.* ; Lernmark, Å.* ; Rewers, M.J.* ; Steck, A.K.* ; She, J.X.* ; Akolkar, B.* ; Robertson, C.C.* ; Onengut-Gumuscu, S.* ; Rich, S.S.* ; Bonifacio, E.* ; Ziegler, A.-G. ; The Teddy Study Group*

Genetic contribution to the divergence in type 1 diabetes risk between children from the general population and children from affected families.

Diabetes 68, 847-857 (2019)

Publ. Version/Full Text

Postprint

Research data

DOI

PMC

	Open Access Green

Abstract
Metrics
Extra information

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.

Altmetric

Additional Metrics?

[➜Log in]