Bonifacio E, et al. - Authors ascertained to what extent the genetic scores (2 previous genetic scores and a merged genetic score) could improve the prediction of type 1 diabetes among genetically at-risk children between 1 September 2004 and 28 February 2010. Data demonstrated that a type 1 diabetes genetic score detected infants without a family history of type 1 diabetes who had a greater than 10% risk for pre-symptomatic type 1 diabetes, and a nearly 2-fold higher risk compared to children identified by high-risk HLA genotypes alone.

Methods

• In the Environmental Determinants of Diabetes in the Young (TEDDY) study, genetically at-risk children were followed at 3- to 6-monthly intervals from birth for the development of islet autoantibodies and type 1 diabetes.
• Between 1 September 2004 and 28 February 2010 infants were recruited and monitored until 31 May 2016.
• Researchers determined the risk (positive predictive value) for developing multiple islet autoantibodies (pre-symptomatic type 1 diabetes) and type 1 diabetes in 4,543 children who had no first-degree relatives with type 1 diabetes and either a heterozygous HLA DR3 and DR4-DQ8 risk genotype or a homozygous DR4-DQ8 genotype, and in 3,498 of these children in whom genetic scores were estimated from 41 single nucleotide polymorphisms.

Results

• Findings disclosed that the risk for developing multiple islet autoantibodies was 5.8% (95% CI 5.0%-6.6%) by age 6 years, and risk for diabetes by age 10 years was 3.7% (95% CI 3.0%-4.4%) in children with the HLA risk genotypes.
• It was determined that the risk for developing multiple islet autoantibodies was 11.0% (95% CI 8.7%-13.3%) in children with a merged genetic score of >14.4 (upper quartile; n = 907) vs 4.1% (95% CI 3.3%-4.9%, P < 0.001) in children with a genetic score of ≤14.4 (n = 2,591).
• In children with a merged score of >14.4, the risk for developing diabetes by age 10 years was 7.6% (95% CI 5.3%-9.9%) compared with 2.7% (95% CI 1.9%-3.6%) in children with a score of ≤14.4 (P < 0.001).
• Among 173 children with multiple islet autoantibodies by age 6 years and 107 children with diabetes by age 10 years, 82 (sensitivity, 47.4%; 95% CI 40.1%-54.8%) and 52 (sensitivity, 48.6%, 95% CI 39.3%-60.0%), respectively, displayed a score >14.4.
• Higher scores were illustrated in European vs US children (P=0.003).
• Data exhibited that in children with a merged score of >14.4, similar risk for multiple islet autoantibodies was yielded and it was consistently >10% in Europe and in the US.
• Greater risk was brought to light in males compared to females (P=0.01).