Implementation of type 1 diabetes genetic risk screening in children in diverse communities: the Virginia PrIMeD project

Background: Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing.

Methods: Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings. Recruiters in each clinic obtained informed consent/assent, a medical history, and a saliva sample for DNA extraction in children with and without a history of T1D. A custom genotyping panel was used to define T1D genetic risk based upon associated SNPs in European- and African-genetic ancestry. Subjects at "high genetic risk" were offered a separate blood collection for screening four islet autoantibodies. A follow-up contact (email, mail, and telephone) in one half of the participants determined interest and occurrence of subsequent T1D.

Results: A total of 3818 children aged 2-16 years were recruited, with 14.2% (n = 542) having a "high genetic risk." Of children with "high genetic risk" and without pre-existing T1D (n = 494), 7.0% (34/494) consented for autoantibody screening; 82.4% (28/34) who consented also completed the blood collection, and 7.1% (2/28) of them tested positive for multiple autoantibodies. Among children with pre-existing T1D (n = 91), 52% (n = 48) had a "high genetic risk." In the sample of children with existing T1D, there was no relationship between genetic risk and age at T1D onset. A major factor in obtaining islet autoantibody testing was concern over SARS-CoV-2 exposure.

Conclusions: Minimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection.