Suchergebnisse

AbstractA consistent finding from twin studies is that the environment shared by family members does not contribute to the variation in susceptibility to asthma. At the same time, it is known that environmental risk factors that are shared by family members are associated with the liability for asthma. We hypothesize that the absence of a main effect of shared environmental factors in twin studies can be explained by gene–environment interaction, that is, that the effect of an environmental factor shared by family members depends on the genotype of the individual. We explore this hypothesis by modeling the resemblance in asthma liability in twin pairs as a function of various environmental risk factors and test for gene–environment interaction. Asthma data were obtained by parental report for nearly 12,000 5-year-old twin pairs. A series of environmental risk factors was examined: birth cohort, gestational age, time spent in incubator, breastfeeding, maternal educational level, maternal smoking during pregnancy, current smoking of parents, having older siblings, and amount of child care outside home. Results revealed that being a boy, born in the 1990s, premature birth, longer incubator time, and child care outside home increased the risk for asthma. With the exception of premature birth, however, none of these factors modified the genetic effects on asthma. In very premature children shared environmental influences were important. In children born after a gestation of 32 weeks or more only genetic factors were important to explain familial resemblance for asthma.

AbstractSeveral studies report caesarean section (CS) to be a risk factor for childhood asthma. We used data from a large cohort of 5-year-old twins to examine the relationship between mode of birth delivery and asthma. The extent to which an infant is exposed to maternal vaginal flora may protect against the risk of developing asthma. Therefore, we expect a lower rate of asthma in twins born by vaginal delivery (VD) than those born by CS, and a lower rate of asthma in first-born twins compared to second-born twins by VD. Information on mode of delivery was obtained at the time of birth in a survey completed by the mother shortly after delivery. Information on history of asthma diagnosis by a physician was obtained by parental report when the twins were 5 years old. Complete data were available for 6330 first-born and 5438 second-born twins from birth cohorts 1991–2000. Full term first-born twins born by CS had a significantly higher risk of asthma compared to those born by VD, odds ratio = 1.59 (95% CI = 1.23–2.06). No significant differences were observed between CS and VD first-born twins when gestational age was less than 37 weeks, and no significant differences were observed between CS and VD second-born twins at any gestational age. No differences in asthma prevalence were found between first- and second-born twins both born by VD. CS may increase the risk of asthma to full term infants, however, the underlying mechanism is unclear.

AbstractMore boys than girls with attention deficit hyperactivity disorder (ADHD) receive treatment. One explanation for this bias may be that boys score higher on disruptive behavior scales than girls. Although this was supported by findings in clinical samples, recent studies in nonreferred samples showed that boys and girls with ADHD are similar with respect to their levels of disruptive behavior as reported by their mother. In this report, we investigate whether the difference in treatment rate is associated with higher teacher problem scores in boys with ADHD than in girls with ADHD. Data were obtained from mothers and teachers in a nonreferred sample of 283 boys and 291 girls with and without ADHD. Children were selected when they scored either low (controls) or high (probands) on attention problems. Mothers completed DSM-IV interviews, Child Behavior Checklists (CBCL) and the Conners Rating Scale (CRS). Teachers filled in the Teacher Report Form (TRF), and the CRS. Boys and girls with ADHD had similar levels of psychiatric illness and school impairment (such as being held back, special class placement and learning problems) by mother report. Mothers reported similar levels of aggression and attention problems in boys and girls with ADHD. In contrast, teachers consistently rated boys with ADHD as having higher scores on reports of attention problems and aggression than girls with ADHD. Gender differences vary across settings: boys and girls with ADHD are rated as behaving differently at school, but not at home. The higher level of teacher reported problem behavior at school may explain the high male–female ratio for ADHD in clinical settings. These findings have implications for the results of genetic studies that rely on referred samples, as these studies may give a distorted view of sex differences in the population.

AbstractWe study the situation in which a cheap measure (X) is observed in a large, representative twin sample, and a more expensive measure (Y) is observed in a selected subsample. The aim of this study is to investigate the optimal selection design in terms of the statistical power to detect genetic and environmental influences on the variance of Y and on the covariance of X and Y. Data were simulated for 4000 dizygotic and 2000 monozygotic twins. Missingness (87% vs. 97%) was then introduced in accordance with 7 selection designs: (i) concordant low + individual high design; (ii) extreme concordant design; (iii) extreme concordant and discordant design (EDAC); (iv) extreme discordant design; (v) individual score selection design; (vi) selection of an optimal number of MZ and DZ twins; and (vii) missing completely at random. The statistical power to detect the influence of additive and dominant genetic and shared environmental effects on the variance of Y and on the covariance between X and Y was investigated. The best selection design is the individual score selection design. The power to detect additive genetic effects is high irrespective of the percentage of missingness or selection design. The power to detect shared environmental effects is acceptable when the percentage of missingness is 87%, but is low when the percentage of missingness is 97%, except for the individual score selection design, in which the power remains acceptable. The power to detect D is low, irrespective of selection design or percentage of missingness. The individual score selection design is therefore the best design for detecting genetic and environmental influences on the variance of Y and on the covariance of X and Y. However, the EDAC design may be preferred when an additional purpose of a study is to detect quantitative trait loci effects.

AbstractIndividual differences in educational attainment (EA) and physical health, as indexed by body mass index (BMI), are correlated within individuals and across generations. The aim of our study was to assess the transmission of these traits from parents to their offspring in childhood and adolescence. We analyzed BMI and EA in 13,916 families from the Netherlands. Data were available for 27,577 parents (mean age 33) and 26,855 of their offspring at 4 and 12 years of age. We employed structural equation modeling to simultaneously estimate the phenotypic transmission of BMI and EA from parents to offspring, the spousal correlations, and the residual child BMI-EA associations after accounting for intergenerational transmission and testing for gender differences therein. We found a significant intergenerational transmission of BMI to BMI in childhood (age 4; standardized regression coefficient β = .10) and adolescence (age 12; β = .20), and of EA to academic achievement in adolescence (β = .19). Cross-trait parent-to-offspring transmission was weak. All transmission effects were independent of parent or offspring gender. We observed within-person EA-BMI correlations that were negative in parents (∼−.09), positive in children (∼.05) and negative in adolescents (∼−.06). Residual EA-BMI were positive in children (∼.05) and insignificant in adolescents. Spousal correlations were .46 for EA, .21 for BMI, and ∼−.09 cross-trait. After accounting for spousal correlations, the intergenerational transmission for BMI and EA is mainly predictive within, but not across, traits. The within-person correlation between BMI and EA can change in direction between childhood and adulthood.

The aim of the present article was to study the prevalence and the heritability of the initiation of breastfeeding in the Netherlands. The study was carried out in 5,581 participants from the Netherlands Twin Register, and included female twins, their sisters and mothers. All of the participants were born between 1911 and 1991. Breastfeeding was self-reported by the participants, and its prevalence was estimated conditional on birth cohort (born before 1955, 1955–1964, 1965–1974, 1975, or later). To estimate the heritability, we conducted extended twin-family modeling using the SEM package OpenMx in R. Mothers of twins had lower prevalence to initiate breastfeeding and the prevalence of initiation of breastfeeding increased with birth cohort: among mothers of twins 66% in the oldest (pre-1955) to 74% in the youngest (post-1974) and among mothers, who were twins themselves or sisters of twins, 79% in the oldest (pre-1955) to 85% in the youngest (post-1974). When accounting for prevalence differences between mothers of twins and other women, heritability of initiation of breastfeeding was 70%. However, the familial resemblance for sister and mother-daughter pairs was clearly lower than for DZ twin pairs, but as the number of non-twin sisters was relatively low, this observation did not lead to a significant contribution of a special shared twin environment.

We consider estimation and testing of linkage equilibrium from genotypic data on a random sample of sibs, such as monozygotic and dizygotic twins. We compute the maximum likelihood estimator with an EM‐algorithm and a likelihood ratio statistic that takes the family structure into account. As we are interested in applying this to twin data we also allow observations on single children, so that monozygotic twins can be included. We allow non‐zero recombination fraction between the loci of interest, so that linkage disequilibrium between both linked and unlinked loci can be tested. The EM‐algorithm for computing the maximum likelihood estimator of the haplotype frequencies and the likelihood ratio test‐statistic, are described in detail. It is shown that the usual estimators of haplotype frequencies based on ignoring that the sibs are related are inefficient, and the likelihood ratio test for testing that the loci are in linkage disequilibrium.

AbstractThe etiology of individual differences in general verbal ability, verbal learning and letter and category fluency were examined in two independent samples of 9‐ and 18‐year‐old twin pairs and their siblings. In both age groups, we observed strong familial resemblance for general verbal ability and moderate familial resemblance for verbal learning, letter and category fluency. All familial resemblance was explained by genetic factors. There was significant covariance among the tests, which was stronger in magnitude in the adolescent cohort. The covariance was mainly explained by genetic effects shared by subtests, both in middle childhood and in late adolescence. In addition to a shared set of genes that influenced all phenotypes, there were also genetic influences specific to the different verbal phenotypes.