Feasibility of genetic and immunological prediction of Type I diabetes in a population-based birth cohort

Aims/hypothesis. Population-wide genetic screening of susceptibility to mul tifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified. Methods. Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the at-risk children to frequent autoantibody follow-up were studied. Screenin g was offered to all families. The infants with HLA-DQB1 genotypes *02/*030 2 and *0302/x (x not equal *02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of beta -cell autoimmunity were invited to a separate prevention trial. Results. The parents of 31526 babies born between November 1994 and April 1 999 (94.4 % of those eligible) agreed to genetic screening. We found that 4 651 infants (14.8 %) had increased genetic risk (2.5 to 15 times that of th e general population) for Type I (insulin-dependent) diabetes mellitus, and 80 % of them joined the autoantibody surveillance. At the age of 1, 2, 3 a nd 4 years, 74, 69, 68 and 76 % of the at-risk children, respectively, atte nded the follow-up. A total of 17 of the 22 children (77 %) who were born d uring the study period and have developed diabetes carry the risk genotypes we currently use for screening. Conclusions/interpretation. Population-based screening of genetic susceptib ility for Type I diabetes, linked with a possibility to participate later i n a prevention trial, is highly accepted in Finland and identifies about 75 % of those developing diabetes at an early age. Families adhere well to th e frequent measurement of signs of beta -cell autoimmunity in the children at-risk.