Subpopulation difference scanning: a strategy for exclusion mapping of susceptibility genes.

BACKGROUND: Association mapping is a common strategy for finding disease-related genes in complex disorders. Different association study designs exist, such as case-control studies or admixture mapping. METHODS: We propose a strategy, subpopulation difference scanning (SDS), to exclude large fractions of the genome as locations of genes for complex disorders. This strategy is applicable to genes explaining disease incidence differences within founder populations, for example, in cardiovascular diseases in Finland. RESULTS: The strategy consists of genotyping a set of markers from unrelated individuals sampled from subpopulations with differing disease incidence but otherwise as similar as possible. When comparing allele or haplotype frequencies between the subpopulations, the genomic areas with little difference can be excluded as possible locations for genes causing the difference in incidence, and other areas therefore targeted with case-control studies. As tests of this strategy, we use real and simulated data to show that under realistic assumptions of population history and disease risk parameters, the strategy saves efforts of sampling and genotyping and most efficiently detects genes of low risk--that is, those most difficult to find with other strategies. CONCLUSION: In contrast to admixture mapping that uses the mixing of two different populations, the SDS strategy takes advantage of drift within highly related subpopulations.

The incidence of type 1 diabetes among children in Finland--rural-urban difference.

The aim of the study was to investigate the incidence of type 1 diabetes among children aged 14 years or under according to the level of urbanization of the place of residence of children at the time of diagnosis in Finland during 1987 to 1996. The analysis was carried out using a Bayesian approach and GIS. The incidence was the highest in the rural heartland areas while the increase in incidence was sharpest in urban areas. The level of urbanization seems to explain only a part of the spatial variation in the incidence in Finland. It is possible that some environmental risk factors for type 1 diabetes have been more prevalent in rural heartland areas than in the rest of the country. These factors might have increased in urban environments in Finland particularly during the first half of 1990s.

A high incidence of type 1 diabetes and an alarming increase in the incidence of type 2 diabetes among young adults in Finland between 1992 and 1996.

AIMS/HYPOTHESIS: The aim of this study was to examine the incidence and trends of type 1 and type 2 diabetes in the 15-39 year-old population between 1992 and 1996 in Finland. SUBJECTS AND METHODS: Data on the nationwide incidence of diabetes were obtained from four data sources: standardised reports from diabetes nurses, the Finnish National Hospital Discharge Register, the Drug Reimbursement Register and the Drug Prescription Register. The inclusion criterion was consistency in the diagnosis of diabetes across at least two data sources. The sex- and age-specific incidence was calculated for 5-year age groups, both for type 1 and type 2 diabetes. The effects of age, sex and year of diagnosis were assessed by fitting the linear regression model to the incidence data. RESULTS: Between 1992 and 1996 the age-adjusted incidence of type 1 diabetes among 15-39 year olds was 15.9 per 100,000/year. The incidence was highest among the 15-19 year olds and decreased with age. Conversely, the incidence of type 2 diabetes was very low among 15-19 year olds and increased with age. The total age-adjusted incidence of type 2 diabetes among 15-39 year olds was 11.8 per 100,000/year. The average annual increase in the incidence of type 2 diabetes was 7.9% (95% CI 3.7-12.2%). CONCLUSIONS/INTERPRETATION: The age at which the Finnish population is at risk of type 1 diabetes extends into young adulthood. The rapid increase in the incidence of type 2 diabetes in the young adult population is a current public health problem.

The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults.

AIMS/HYPOTHESIS: The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15-39 years. METHODS: Data on all cases of type 1 diabetes (n = 1,345) and type 2 diabetes (n = 1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from diabetes nurses, the National Hospital Discharge Register, the Drug Prescription Register and the Drug Reimbursement Register. Information on matched controls and the family members of all study subjects were obtained from the National Population Registry. The odds ratios (ORs) for both types of diabetes were estimated using a conditional logistic regression model. RESULTS: There was a U-shaped relationship between maternal age and the risk of type 2 diabetes in the offspring: the risk was higher in children born to young and old mothers compared with children born to mothers aged around 30 years. The children born second (OR 0.76, 95% CI 0.62-0.94), third (OR 0.73, 95% CI 0.55-0.95), or fourth (OR 0.66, 95% CI 0.47-0.94) had a lower risk of type 2 diabetes than the first-born children. Maternal age, paternal age, and birth order did not have an effect on the risk of type 1 diabetes in the individuals aged 15-39 years at the time of diagnosis. CONCLUSIONS/INTERPRETATION: Maternal age and birth order are both associated with the risk of early-onset type 2 diabetes. However, part of these associations may be due to low birthweight. In this study neither parental age nor birth order showed a significant association with the risk of type 1 diabetes diagnosed after 15 years of age.

Zinc and nitrate in the ground water and the incidence of Type 1 diabetes in Finland.

AIMS: In Finland, the risk of childhood Type 1 diabetes varies geographically. Therefore we investigated the association between spatial variation of Type 1 diabetes and its putative environmental risk factors, zinc and nitrates. METHODS: The association was evaluated using Bayesian modelling and the geo-referenced data on diabetes cases and population. RESULTS: Neither zinc nor nitrate nor the urban/rural status of the area had a significant effect on the variation in incidence of childhood Type 1 diabetes. CONCLUSIONS: The results showed that although there was no significant difference in incidence between rural and urban areas, there was a tendency to increasing risk of Type 1 diabetes with the increasing concentration of NO3 in drinking water. The fact that no significant effect was found may stem from the aggregated data being too crude to detect it.