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)
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.
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Times Cited
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Islet Autoantibodies; Susceptibility; Sarcoidosis; Expression; Haplotypes; Prediction
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2019
Prepublished im Jahr
HGF-Berichtsjahr
2019
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 68,
Heft: 3,
Seiten: 847-857
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
American Diabetes Association
Verlagsort
Alexandria, VA.
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30201 - Metabolic Health
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e)
G-502100-001
G-503800-001
Förderungen
Copyright
Erfassungsdatum
2019-03-07