Phenotype mining in CNV carriers from a population cohort.

Phenotype mining is a novel approach for elucidating the genetic basis of complex phenotypic variation. It involves a search of rich phenotype databases for measures correlated with genetic variation, as identified in genome-wide genotyping or sequencing studies. An initial implementation of phenotype mining in a prospective unselected population cohort, the Northern Finland 1966 Birth Cohort (NFBC1966), identifies neurodevelopment-related traits-intellectual deficits, poor school performance and hearing abnormalities-which are more frequent among individuals with large (>500 kb) deletions than among other cohort members. Observation of extensive shared single nucleotide polymorphism haplotypes around deletions suggests an opportunity to expand phenotype mining from cohort samples to the populations from which they derive.

Maternal hypertensive disorders during pregnancy and mild cognitive limitations in the offspring.

BACKGROUND: It remains unclear whether maternal hypertensive disorders could impact cognitive development of the child. The aim of this study was to explore the association between hypertensive disorders and other maternal biological and social factors on the risk of mild cognitive limitations (intelligence quotient 50-85) in the offspring. METHODS: An 11.5-year follow-up study of the Northern Finland Birth Cohort 1986 (n = 9432) was utilised. The analysis included 8847 singleton children, of whom 198 had mild cognitive limitations. Gestational hypertension was defined as de novo hypertension (blood pressure ≥ 140/90), diagnosed mid-pregnancy in a previously normotensive woman. Data on intelligence level of the children were based on standardised intelligence test results. RESULTS: Eleven per cent (n = 20) of mothers having a child with mild cognitive limitations had gestational hypertension. Maternal gestational hypertension was independently associated with increased odds of mild cognitive limitation in the offspring (odds ratio 2.4 [95% confidence interval 1.4, 3.9]). Other independent maternal risk factors for mild cognitive limitation were high pre-pregnancy body mass index (≥30 kg/m(2)), multiparity (≥4) and low education. In addition family's socio-economic status lower than professional, male gender and small birthweight-for-gestational age appeared as independent risk factors for mild cognitive limitation. CONCLUSIONS: Gestational hypertension should be considered as one of the adverse early risk factors that may predispose to impaired cognitive development in childhood.

Variations in prenatal sociodemographic factors associated with intellectual disability: a study of the 20-year interval between two birth cohorts in northern Finland.

The authors followed two cohorts of children born in northern Finland in 1966 (n = 12,058) and 1985-1986 (n = 9,432) to examine whether associations between maternal sociodemographic factors assessed during pregnancy and intellectual disability in the offspring changed over a 20-year interval. Both of the cohorts were followed up to the age of 11.5 years using similar methods and definitions of intellectual disability. Data on sociodemographic factors were based on comparable questionnaires returned by the mothers during the 25th week of gestation. Despite an interval of 20 years between the cohorts, the main indicators of socioeconomic disadvantage and maternal multiparity remained as having the largest impact on the incidence of intellectual disability, while single factors such as older maternal age at delivery, being single, and living in a remote area lost their association with intellectual disability. Over 20 years, prepregnancy maternal obesity (body mass index > or =30) became a newly associated factor (adjusted odds ratio = 2.8, 95% confidence interval: 1.5, 5.3). A future challenge is to explore the mediating mechanisms between intellectual disability and its associated preventable intergenerational environmental or lifestyle factors.

Etiological survey on intellectual disability in the northern Finland birth cohort 1986.

The etiology of intellectual disability was studied both in incident (n = 9,432) and prevalent (n = 9,351) populations in a one-year birth cohort born in Northern Finland in 1985-1986. Data from multiple sources were used to follow the children until the age of 11.5 years. Of the incident cases (n=119) with intellectual disabilities, 66.4% had etiologically biomedical associative factor. Paranatal factors were relatively fewer and prenatal more common compared with earlier studies. We found nearly double the prevalence of genetic factors leading to intellectual disabilities compared with a contemporary study from Norway. The differences between the populations, despite random variation, some dissimilarities between etiological categorization and diagnostic accuracy, are in most part due to true differences between the study populations and genetic pool.

Temporal changes in incidence and prevalence of intellectual disability between two birth cohorts in Northern Finland.

We followed two separate, genetically homogeneous cohorts of children born in 1966 (n = 11,965) and 1985-1986 (n = 9,432) in Northern Finland to determine temporal changes in the incidence and prevalence of subcategories of intellectual disability within the same geographic area. The children were followed up to the age of 11.5 years. Similar study design, data ascertainment methods, and definition of intellectual disability were used. There was no change in the total incidence (12.62/1,000 in each) or in total prevalence (11.03/1,000 vs. 11.23/1,000) of intellectual disability. However, in the subcategories of intellectual disability, there was a shift from severe and moderate towards mild; whereas profound intellectual disability remained at the same level. The temporal changes followed generally similar patterns by gender.