Investigating genomic imprinting and susceptibility to insulin-dependent diabetes mellitus: an epidemiologic approach.

Children of fathers with insulin-dependent diabetes mellitus (IDDM) are at greater risk of developing the disease than are children of IDDM mothers, reasons for which are currently unknown. To explore the possibility that genomic imprinting contributes to this phenomenon, 1,774 families with at least one IDDM child diagnosed before the age of 17 years and between 1950 and 1981 from the Children's Hospital at Pittsburgh IDDM Registry were evaluated. Approximately 1% of the mothers and 2.9% of the fathers were reported to have IDDM diagnosed before the age of 36 years (P less than 0.001). Excluding IDDM probands, the IDDM recurrence risk to siblings in families with an IDDM father was greater than that in families with an IDDM mother or in those with neither parent affected. Lifetable analyses revealed that among all children of diabetic fathers (probands included), there was a greater prevalence of IDDM, through age 30 years, for sons compared to daughters (59.5% vs. 34.1%, P = 0.02). However, there was no significant sex difference in the prevalence of IDDM among children of affected mothers (41.1% vs. 45.5%, P greater than 0.05). These data are not consistent with the genomic imprinting hypothesis and suggest that other genetic and/or environmental factors contribute to the increased risk for children of IDDM fathers.