medwireNews: Type 1 diabetes that develops in adulthood has weaker familial associations than type 1 diabetes that develops in childhood, confirm findings from a Swedish cohort study.
Yuxia Wei (Karolinska Institutet, Stockholm, Sweden) and colleagues explain in The Lancet Diabetes & Endocrinology that it has already been suggested that adult-onset type 1 diabetes is “less heritable,” given that “individuals with adult-onset type 1 diabetes seem to have fewer high-risk human leukocyte antigen (HLA) genotypes and lower genetic risk scores than individuals with childhood-onset type 1 diabetes.”
Further to this, Wei et al now show that a family history of paternal type 1 diabetes is more common in both adult-onset cases and childhood-onset cases, affecting 2.0% and 3.3% of cases, respectively, than is a family history of maternal type 1 diabetes, at 1.1% and 2.0%, respectively.
“This finding might reflect preferential transmission of high-risk genes from fathers and the effect of parental origin on how genes are expressed,” say the researchers.
The study included linked information from several Swedish national registers for 2,943,832 people born in Sweden between 1982 and 2010. Information on diagnosis of adult-onset type 1 diabetes between the ages of 19 and 30 years was assessed for 1,805,826 individuals and on childhood-onset cases by the age of 18 years for 2,832,755 individuals.
Overall, 3240 people developed adult-onset type 1 diabetes at a mean age of 23.4 years, of whom 59.7% were male and 40.2% were female, while 17,914 individuals developed type 1 diabetes in childhood at a mean age of 9.8 years, of whom 54.8% were male and 45.2% were female.
The incidence of type 1 diabetes in adults and children was 2.1 and 3.7 per 10,000 person–years, respectively, with a corresponding 0.2% and 0.7% of the population developing the condition.
Compared with people without any first-degree relatives with type 1 diabetes, those with an affected first-degree relative were a significant 7.21 times more likely to develop adult-onset and 9.92 times more likely to develop childhood-onset type 1 diabetes.
This weaker heritable relationship with adult-onset versus childhood-onset type 1 diabetes was true irrespective of whether individuals had an affected mother (HR=5.22 vs 7.35), father (HR=7.71 vs 9.75) or full sibling (8.12 vs 11.30), report the researchers.
Quantitative genetic analysis indicated that heritability of adult-onset type 1 diabetes was lower than that for childhood-onset type 1 diabetes, and estimated to be 56% versus 81%, with non-shared environmental components contributing 44% and 19% towards type 1 diabetes development, respectively.
Noting these observations, the researchers point out that “the influence of environmental factors is more prominent for adult-onset type 1 diabetes than childhood-onset type 1 diabetes, emphasising the potential for preventive interventions targeting these factors.”
The unique environmental factors specific to a person could include lifestyle choices developed during adulthood contrary to common familial factors shared among siblings like socioeconomic status or diet during childhood, they explain.
Commenting on the findings in a related editorial, Richard Leslie, from the Barts and Royal London Medical School in the UK, says: “Two important points derive from these results. First, that environmental (strictly non-genetic) factors causing type 1 diabetes are probably important and often unique, and second, the nature of such nongenetic factors [is] unclear.”
He continues: “The lower heritability in older-onset cases does raise the potential of greater therapeutic success, plus the intriguing prospect of identifying those unknown unique non-genetic factors associated with adult-onset type 1 diabetes.”
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Lancet Diabetes Endocrinol 2024; doi:10.1016/S2213-8587(24)00068-8
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