Genetic susceptibility in the relative maternal protection from type 1 diabetes

Authors:
  • SSSarah D. Slack
    Sarah D. Slack
  • NVNeha Venkatesh
    Neha Venkatesh
  • SRShane E. Ridoux
    Shane E. Ridoux
  • KHKirk R. Hohsfield
    Kirk R. Hohsfield
  • LVLauren A. Vanderlinden
    Lauren A. Vanderlinden
  • JNJill M. Norris
    Jill M. Norris
  • RJRandi K. Johnson
    Randi K. Johnson
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Abstract
Objective: Type 1 diabetes is half as common in offspring of affected mothers versus fathers. We investigated whether selective loss of fetuses with high genetic risk during type 1 diabetes pregnancy explains this relative protection.Research Design and Methods: In 6942 TEDDY cohort live births, we compared genetic susceptibility by type 1 diabetes-affected family member and tested if it explained maternal protection from diabetes or its preclinical stages.Results: The GRS2x did not differ between children with affected mothers (P=0.36) or siblings (P=0.27) versus fathers. Relative maternal protection from type 1 diabetes and islet autoimmunity (IA) was observed with GRS2x adjustment (diabetes HR: 0.50, P=0.01; IA HR: 0.38, P=0.006) and without adjustment but not during progression from IA to diabetes. This protection wanes after age 6 years.Conclusions: Intrauterine exposure to type 1 diabetes offers relative protection from IA during early childhood and is not explained by genetic susceptibility differences.
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