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Intrauterine factors important for cognitive development, such as birth weight, chorionicity and umbilical cord characteristics were investigated. A total of 663 twin pairs completed the Wechsler Intelligence Scale for Children-Revised and scores were available for Performance, Verbal and Total Intelligence Quotient (IQ). The intrauterine factors examined were birth weight, placental weight and morphology, cord knots, cord length and cord insertion. IQ scores for the varying levels of the intrauterine markers adjusting for gender and gestational age were calculated. The heritability of IQ and the association between IQ and intrauterine environment were examined. Twins with lower birth weight and cord knots had lower IQ scores. The aetiology of IQ is largely distinct from that of birth weight and cord knots, and non-shared environment may influence the observed relationships. [ABSTRACT FROM PUBLISHER]

To extract functional information on genes and processes from large expression datasets, analysis methods are required that can computationally deal with these amounts of data, are tunable to specific research questions, and construct classifiers that are not overspecific to the dataset at hand. To satisfy these requirements, a stepwise procedure that combines elements from principal component analysis and discriminant analysis, was developed to specifically retrieve genes involved in processes of interest and classify samples based upon those genes. In a global expression dataset of 300 gene knock-outs in Saccharomyces cerevisiae, the procedure successfully classified samples with similar 'cellular component' Gene Ontology annotations of the knock-out gene by expression signatures of limited numbers of genes. The genes discriminating 'mitochondrion' from the other subgroups were evaluated in more detail. The thiamine pathway turned out to be one of the processes involved and was successfully evaluated in a logistic model to predict whether yeast knock-outs were mitochondrial or not. Further, this pathway is biologically related to the mitochondrial system. Hence, this strongly indicates that our approach is effective and efficient in extracting meaningful information from large microarray experiments and assigning functions to yet uncharacterized genes. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Recently, Swedish members of the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) provided evidence that smoking may trigger RA-specific immune reactions to citrullinated protein in carriers of HLA-DR shared epitope alleles. In an effort to confirm this interaction between smoking and shared epitope alleles, we performed a case-only analysis of 3 North American RA cohorts. METHODS: A total of 2,476 white patients with RA were studied, 1,105 from the North American Rheumatoid Arthritis Consortium (NARAC) family collection, 753 from the National Inception Cohort of Rheumatoid Arthritis Patients (Inception Cohort), and 618 from the Study of New Onset Rheumatoid Arthritis (SONORA). All patients were HLA-DRB1 typed, and tested for anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor. Information about smoking history was obtained by questionnaire. RESULTS: A significant association was found between smoking and the presence of anti-CCP in the NARAC and the Inception Cohort, but not in the SONORA. The shared epitope alleles consistently correlated with anti-CCP in all 3 populations. Using multiple logistic regression analyses, shared epitope alleles were still the most significant risk factor for anti-CCP positivity. Weak evidence of gene-environment interaction between smoking and shared epitope alleles for anti-CCP formation was found only in the NARAC. CONCLUSION: Unlike the EIRA data, we could not confirm a major gene-environment interaction for anti-CCP formation between shared epitope alleles and smoking in 3 North American RA cohorts. Our data indicate a need for further studies to address the full range of environmental factors other than smoking that may be associated with citrullination and RA. [ABSTRACT FROM AUTHOR]

The aim of this study is to quantify the genetic and environmental variation in biological parameters of the adolescent growth in stature in both sexes, using structural equation models. Standing height was measured in 99 twin pairs from the Leuven Longitudinal Twin Study. Subjects were seen at semi-annual intervals between 10 and 16 years and at 18 years. Preece-Baines model I was fitted to the individual data and biologically meaningful parameters were derived. Path models were fitted to these parameters and a gender heterogeneity analysis was performed. A model including additive genetic and specific environmental factors (AE-model), allowing for a difference in total variance or in genetic/environmental variance components in males and females best explains most of the growth characteristics. For the timing and velocity of the adolescent growth spurt, no gender heterogeneity was observed, and the genetic (0.89 to 0.93) and specific environmental (0.07 to 0.11) contributions were equal in both sexes. For stature at take-off, stature at peak height velocity and for adult stature, gender heterogeneity was observed and different models appeared to result in the best fit for boys and girls. For height at PHV and adult stature, the significant contribution of a common environmental (0.39 to 0.56) factor in boys was noteworthy. For percentage of adult stature and distances between relevant time points of the growth curve, a non-scalar effect was observed, indicating that different genes affect these characteristics in boys and girls. It is concluded that most characteristics of the growth spurt in stature are under strong genetic control. Gender heterogeneity is present for stature and for a number of derived growth characteristics. [ABSTRACT FROM AUTHOR]

Objective: (1) To determine by means of multivariate genetic modelling whether the covariation of blood pressure (BP) and body mass index (BMI) is compatible with a direct effect of BMI on BP, or rather with pleiotropy or environmental association, and (2) to quantify the contribution of such an effect and of heritability and environmental factors to BP variance. Design and methods: Fifty monozygous and 41 dizygous male twin pairs (ages: 17-38 years) were studied. BMI was calculated as weight/height[SUP2]. Blood pressure was the mean of three conventional measurements in the supine position. Estimates for the path coefficients of the three hypothesised models were obtained using Maximum Likelihood Estimation and were used to calculate the predicted covariance matrices for these models. A &khgr;[SUP2] goodness-of-fit index of P > 0.05 indicated an adequate fit. Likelihood ratio &khgr;[SUP2] statistics and the Akaike Information Criterion (AIC) were used to choose the best model among the fitting models. The path coefficients of the best model were used to estimate the variance decomposition of BP. Results: All hypothesised models fitted the data. The AIC was lowest for the model representing an influence of BMI on BP, for both systolic (AIC = -22.3) and diastolic (AIC = -22.2) BP. The estimated percentages of the total phenotypic variance of BP, which could be explained by the influence of BMI on BP, were 11.4% and 12.9% for systolic and diastolic pressure respectively. The remaining variances were associated with variation in genetic and environmental factors. Conclusions: A direct influence of BMI on BP constitutes the most likely explanation of the BP-BMI-covariation and it accounts for about 12% of the BP-variance in young healthy men. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to examine the regulation of fetal serum concentrations of insulin (C-peptide), insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, which are growth-regulating factors in the fetus, in monozygotic and dizygotic twin pairs.Study Design: Cord serum samples were collected from 110 twin pairs and compared with 178 nonsibling singleton pairs with the same gestational age. Five twin pairs were excluded from the statistical analyses because of severe intrauterine growth restriction and placental abnormalities in one. Zygosity was assigned by histologic examination of the placenta and by a questionnaire sent to the mother when the twins were > or = 6 months old. Analyses included the calculation of correlation coefficients, between-pair variation, and univariate genetic analysis.Results: Cord serum C-peptide concentrations were highly correlated in monozygotic (r = 0.94) and dizygotic twins (r = 0.79) but not in singleton pairs (r = -0.05); the between-pair variation was also smaller in twins than in singletons. Genetic analysis demonstrated a large contribution of the common environment to the variance in C-peptide concentrations (80%) and a smaller genetic contribution (12%). Insulin-like growth factor-I concentrations were better correlated in monozygotic (r = 0.82) than in dizygotic twins (r = 0.42), with a smaller between-pair variation in the former group (22% +/- 4% vs 51% +/- 5%). Univariate genetic analysis indicated that insulin-like growth factor-I levels were regulated predominantly by genetic mechanisms (93% in boys and 77% in girls). The regulation of insulin-like growth factor-II was more complex, with a gender-specific genetic contribution (50% for both sexes combined, 63% for girls but only 5% for boys). Insulin-like growth factor binding protein-1 was regulated by genetic mechanisms (41%) and the common environment (32%) but also by the specific or unique environment of each fetus (27%). In all five twins with intrauterine growth restriction of one member insulin-like growth factor binding protein-1 concentrations were markedly higher in the growth-restricted fetus.Conclusions: Insulin secretion in twin fetuses is determined primarily by their common, probably maternal, environment, whereas insulin-like growth factor-I production is predominantly genetically regulated. Insulin-like growth factor-II and insulin-like growth factor binding protein-1 are regulated by both genetic and environmental factors. Of these growth-regulating factors, insulin-like growth factor binding protein-1 appears to be the best marker of intrauterine growth restriction in the individual case. [ABSTRACT FROM AUTHOR]

In a cross-sectional study, children 0-6 yr of age from eight different population groups in Africa and Asia were examined. Clinical assessment defined 8750 children as being well nourished and 194 as having marasmus. Height, weight, arm circumference (AC), and triceps skinfold thickness were measured; the latter two measurements and the clinical assessment were done by the same observer. Based on data from normal children, local growth curves were computed for each group. Each child's growth was expressed in standard deviation scores (SDS) of his own group. On the basis of the results of a discriminant analysis, all variables were ranked by their decreasing power to discriminate between normal and marasmic children. For 83% of the children one measurement (AC/age) is sufficient to classify them definitely; for the others, several variables are needed. This strategy yields an overall sensitivity of 80%, a specificity of 97%, and a positive predictive value of 38%. [ABSTRACT FROM AUTHOR]