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 first-degree 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 type I diabetes in families. Younger age at onset (less than 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.