Contribution of hierarchical clustering techniques to the modeling of the geographic distribution of genetic polymorphisms associated with chronic inflammatory diseases in the Québec population.

OBJECTIVES: The purpose of this project was to evaluate the potential of the downward hierarchical clustering analysis (DHCA) for studying genetic heterogeneity, i.e. differences in allele frequency in subpopulations, such as the 15 public health regions of the province of Québec (Canada). METHODS: The study relied on an anonymized sample of 1,680 individuals who had participated in the Québec Heart Health Survey in 1990-1991. The genotyping of 11 variants in 8 candidate genes known to be involved in chronic inflammatory diseases, namely asthma and cardiovascular diseases, was performed using the amplification refractory mutation system and restriction fragment length polymorphism techniques. Only variants showing an allelic frequency >2% in the Québec Heart Health Survey (n = 8) were selected. DHCA techniques were then applied to model the geographical distribution of these 8 genetic variants in 15 Québec public health regions and to study genetic heterogeneity. RESULTS: The DHCA allowed to group public health regions and gene variants on the basis of genetic variability. For both asthma and cardiovascular diseases, 3 significant clusters of public health regions and 1 cluster of gene variants were identified. DISCUSSION: This study suggests that DHCA might be useful in studying genetic heterogeneity at the population level and for public health activities.

Do children aged 9 through 11 years understand the DISC Version 2.25 questions?

OBJECTIVE: To assess the understanding of Diagnostic Interview Schedule for Children-Version 2.25 (DISC-2.25) questions by children aged 9 through 11 years. METHOD: Two hundred forty children were recruited from four public schools. The cognitive appraisal of 280 questions from the most prevalent DSM-III-R diagnoses was evaluated. The collaboration of four children was necessary to cover one DISC. Sixty DISCs, evenly distributed according to age and sex, were completed. Two child psychiatrists evaluated the children's answers. Nonparametric tests were used to assess understanding of questions as a whole, of time concepts (overall, categories, number), and of questions based on the number of words. RESULTS: Children aged 9, 10, and 11 years understood 38%, 38%, and 42% of the questions as a whole, respectively, and 26%, 24%, and 30% of the overall time concepts, respectively. The understanding rates of questions as a whole were significantly higher than those of overall time concepts. Durations were significantly better understood than periods and frequencies, and questions having one time component were significantly better grasped than those with two or more. Shorter questions were significantly better understood than longer ones. CONCLUSION: Although the DISC has been greatly improved since the initial version, the results suggest that additional revision is needed before clinicians or researchers use the DISC with younger children.

Alzheimer's disease: preliminary study of spatial distribution at birth place.

Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by a progressive loss of memory and the alteration of cognitive functions. At least three chromosomal segments have been associated with early-onset AD in genetic linkage studies. These results argue for a certain degree of heterogeneity in the genetic origin of some forms of AD, although environmental risk factors cannot be ruled out in late-onset AD. In this preliminary study, we analyzed the geographical distribution of the birth places of a sample of 235 AD cases born in a defined region of Quebec (Canada), between 1895 and 1935. We wished to test the hypothesis that risk factors acting at, or around birth place and time play a role in the etiology of AD. The field of study was divided into rural and urban areas. A reference population of live births was used to compute a measure of odds ratio (OR). The OR results showed a statistically significant excess of AD cases in the rural area as compared to the reference population. When stratified for sex, the OR results showed a global excess of female AD cases in both the rural and the urban areas. For men, only the urban area presented a statistically significant deficit. We also analyzed the structures of the genealogical kinships of the rural and urban sub-groups. Although AD cases from the rural sub-group were more closely related to each other than those from the urban one, removal of the kin pairs from the OR analysis seemed to have little effect on the rural/urban distribution of cases. Therefore, the OR results would not appear to be due primarily to a difference in the kinship structures of the two sub-groups. This could mean that some risk factors for AD afflict women more strongly than men, the effect being different depending on the urban or rural origin. However, potential biases such as a higher rate of report for women, differential migration between birth places or a differential mortality ratio between sexes could produce spurious results in the direction of what we have observed in this preliminary study.

Season of birth and Alzheimer's disease: a population-based study in Saguenay-Lac-St-Jean/Québec (IMAGE Project).

The birth distribution of 399 cases of Alzheimer's disease (AD) identified in the region of Saguenay-Lac-St-Jean (Québec) was compared with that of: (a) the population currently living in the area; and (b) the population born during the same period in the same area. AD cases have been recruited since 1986 by the IMAGE Project. Cases and controls were grouped according to the month of birth and according to the day of birth using density estimation. Analyses showed a significant deficit of births in the month of May. We believe these preliminary results deserve further attention and we suggest two possible explanations that could lead to a deficit of AD births at specific periods during the year.

Quebec child mental health survey: prevalence of DSM-III-R mental health disorders.

The Quebec Child Mental Health Survey (QCMHS) was conducted in 1992 on a representative sample of 2400 children and adolescents aged 6 to 14 years from throughout Quebec. Prevalences of nine Axis-I DSM-III-R (American Psychiatric Association, 1987) mental health disorders were calculated based on each informant (for 6-11-year-olds: child, parent, and teacher; for 12-14-year-olds: child and parent). Informant parallelism allows the classification of results of the demographic variables associated with disorders in the logistic regression models. This strategy applies to group variables (correlates of disorders) whereas informant agreement applies to individual diagnoses. Informant parallelism implies that results for two informants or more are in the same direction and significant. In the QCMHS, informant parallelism exists for disruptive disorders, i.e. in two ADHD regression models (child and parent) higher rates among boys and young children, and in three oppositional/conduct disorders regression models (child, parent, and teacher) higher rates among boys. No informant parallelism is observed in the logistic regression models for internalizing disorders, i.e. the patterns of association of demographic variables with anxiety and depressive disorders vary across informants. Urban-rural residence does not emerge as a significant variable in any of the logistic regression models. The overall 6-month prevalences reach 19.9% according to the parent and 15.8% according to the child. The implications of the results for policy makers and clinicians are discussed.