Age-Corrected Empirical Genetic Risk Estimates for First-Degree Relatives of IDDM Patients

Abstract

The families of 554 type I (insulin-dependent) diabetics were genetically analyzed according to probands' sex and age at onset applying a modification of Strömgren's method of age correction. Lifetime recurrence risk of type I diabetes (risk up to age 80 yr) for firstdegree relatives in three consecutive generations was calculated. The overall risk (± 1 SE) for siblings was 6.6 ± 1.1% and for children was 4.9 ± 1.7%. The similar risks among siblings and children argue against a simple autosomal recessive trait. The results do not permit a conclusion about a distinct mode of inheritance. Regardless of age at onset, offspring of male probands always had a higher risk than offspring of female probands. Among all probands, fathers were significantly more often affected with type I diabetes (about twice) than mothers (4.1 ± 0.9 vs. 1.7 ± 0.6%, respectively). The risk for further siblings of the proband was significantly increased in the presence of a type I diabetic parent (25.2 ± 10.3 vs. 5.8 ± 1.0% for remaining probands), indicating a nonrandom clustering of type I diabetes in families. Younger age at onset (<25 yr) was not associated with an increased risk to siblings. Type II diabetes was not more frequent among parents and siblings of type I diabetics than in the general population. The calculated risk estimates are of practical value in genetic counseling and are important for genetic models concerning type I diabetes.