Abstract
BackgroundThe incidence of Type 1 diabetes (T1DM) is increasing fast in many populations. The reasons for this are not known, although an increase in the penetrance of the diabetes-associated alleles, through changes in the environment, might be the most plausible mechanism. After the introduction of insulin treatment in 1930s, an increase in the pool of genetically susceptible individuals has been suggested to contribute to the increase in the incidence of Type 1 diabetes.ResultsTo explore this hypothesis, the authors formulate a simple population genetic model for the incidence change driven by non-Mendelian transmission of a single susceptibility factor, either allele(s) or haplotype(s). A Poisson mixture model is used to model the observed number of cases. Model parameters were estimated by maximizing the log-likelihood function. Based on the Finnish incidence data 1965–1996 the point estimate of the transmission probability was 0.998. Given our current knowledge of the penetrance of the most diabetic gene variants in the HLA region and their transmission probabilities, this value is exceedingly unrealistic.ConclusionsAs a consequence, non-Mendelian transmission of diabetic allele(s)/haplotype(s) if present, could explain only a small part of the increase in incidence in Finland. Hence, the importance of other, probably environmental factors modifying the disease incidence is emphasized.
Highlights
The incidence of Type 1 diabetes (T1DM) is increasing fast in many populations
In this paper we present a simple genetic model in order to evaluate the magnitude of the allele frequency change in time, and by assuming reasonable penetrance probabilities, evaluate the effect on the time trend of the incidence of Type 1 diabetes
Material Data on the new cases of Type 1 diabetes in Finland were obtained from two nationwide sources: new cases between 1965 and 1986 were obtained from the Central Drug Registry of the Social Insurance Institution, and between 1987 and 1996 from the prospective childhood
Summary
The incidence of Type 1 diabetes (T1DM) is increasing fast in many populations. The reasons for this are not known, an increase in the penetrance of the diabetes-associated alleles, through changes in the environment, might be the most plausible mechanism. After the introduction of insulin treatment in 1930s, an increase in the pool of genetically susceptible individuals has been suggested to contribute to the increase in the incidence of Type 1 diabetes. The genetic background is complex, involving a major contribution from the HLA region, and several other genes may be involved, each having a minor effect on disease susceptibility [10,11,12]. The roles for these genes have been difficult to assess because of their small effects and because of the small size (page number not for citation purposes)
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