title: Increasing incidence of Type 1 diabetes--role for genes?
abstract: BACKGROUND
  The 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.
  
  
  RESULTS
  To 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.
  
  
  CONCLUSIONS
  As 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.
authors.affiliation: Department of Mathematics and Statistics, Rolf Nevanlinna Institute, P,O, Box 4 (Yliopistonkatu 5), FIN-00014 University of Helsinki, Finland. janne.pitkaniemi@ktl.fi
authors.forename: Janne
authors.initials: J
authors.lastname: Pitkäniemi
authors.forename: Päivi
authors.initials: P
authors.lastname: Onkamo
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Elja
authors.initials: E
authors.lastname: Arjas
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008957:Models, Genetic; D019683:Penetrance