Pediatr Diabetes. 2020;21(8):14471456. doi: 10.1111/pedi.13122
Family histories suggest strong degrees of inheritance of T1D in some children, especially in populations with an overall high risk of autoimmunity.
This paper from the Finnish T1D Prediction and Prevention (DIPP) study looked at subjects carrying high HLA-conferred risk for T1D. A family history of T1D in relatives outside the core family was a significant risk factor for islet autoimmunity and progression to clinical T1D in HLA susceptible children.
Case children (N=343) were identified when they were found to be positive for at least one islet autoantibody. They were matched by age, gender and class II HLA genotype to control children (N=343) who tested negative for islet autoantibodies at the time of data collection. An extended family history of T1D was obtained using structured questionnaires in all subjects.
Among children who were autoantibody positive and progressed to T1D, 62.2% (28/45) had at least one relative with T1D. Interestingly, more of these children (26/45, 57.8%) had such a relative outside the core family, compared to 30.7% of children with no autoantibodies (P=.001), 35.2% of those with only classical islet cell antibodies (P=0.006), and 35.2% of non-progressors with biochemical autoantibodies (P=0.011). A positive history of T1D in the paternal extended family was more common in children with multiple biochemical autoantibodies compared to those with only one biochemical autoantibody (P=0.010). However, no association was found between the specificity of the first appearing autoantibody and family history of T1D.
These data suggest that in addition to HLA genotypes, other genetic factors play a major role in influencing islet autoimmunity and/or progression to overt T1D.