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.

AbstractOur objective was to examine the overlap between autistic traits and other behavioral problems in a general population sample, and explore the extent to which this overlap is due to genetic or environmental factors. Youth Self Report (YSR) data were collected in a general population sample of 424 twin pairs at 18 years of age, and their nontwin siblings. In 197 of these twin families, self-report ratings on the Autism-spectrum Quotient (AQ) were collected. Stepwise backward regression analyses revealed that of all 8 YSR syndrome scales, the Withdrawn Behavior (WB) and Social Problems (SOC) scale were the most important predictors of AQ scores, and together with sex, explained 23% of the variance in AQ scores. Genetic structural equation modeling showed that the overlap between AQ and WB and SOC was mainly due to genetic effects. About half of the genetic variance in AQ scores was specific to the AQ, with the remaining half shared with genetic variance in WB and SOC. Endorsement of autistic traits in a general population sample is associated with social and withdrawn behavioral problems and these problems partly share a common genetic etiology with autistic traits. However, most of the variance in AQ scores remains unexplained by YSR scores, and half of the genetic variance in AQ is unshared with WB and SOC. These results indicate that autistic traits have specific characteristics that are substantially genetically independent from other common but related behavioral domains such as social problems and withdrawn behavior.

AbstractWe studied the short- and long-term effects of classroom separation in twins on behavior problems and academic performance. Short-term effects were studied at age 7 in twins separated at age 5 and long-term effects at age 12 in twins who had been separated or together most of the time at school. Behavior problems were rated by mothers (Child Behavior Checklist at ages 3, 7 and 12) and teachers (Teacher Report Form at ages 7 and 12). Academic achievement was measured at age 12 using a national academic achievement test (CITO). At age 7, twins from separated pairs had more internalizing and externalizing problems than non- separated twins, as rated by both mothers and teachers. Only for the maternal ratings of internalizing problems, however, could these effects be attributed to the separation itself and not to preexisting problems (at age 3) between separated and nonseparated twins. Long-term effects of separation were significant for maternal and teacher ratings of internalizing and externalizing problems, but these effects could be explained by preexisting differences between separated and nonseparated groups. There were no differences in academic achievement between the separated and nonsepa- rated group. These results suggest that the decision to separate twins when they go to school is based in part on the existing behavioral problems of the twins and that, in the long run, separation does not affect problem behavior or academic achievement. The findings were the same for monozygotic and dizygotic twins.

AbstractIn order to determine if twinning impacted achievement of motor milestones the attainment of early motor milestones in twins was examined and compared to published data from singletons of the same age from the same culture and birth years. We examined the influence of twinning, sex, zygosity and birth cohort (1987–2001) on the motor development of twins aged 0 to 24 months. Data on the attainment of motor milestones (turn, sit, crawl, stand and walk) of twins were collected from maternal reports. All data were corrected for gestational age. Data from the twin sample were compared to normative data from singletons, which were available from Child Health Clinics (CHC). Analyses across twin data and the CHC singleton data revealed no differences between twins and singletons in achievement of motor milestones. Girls were able to sit without support slightly earlier than boys, otherwise there were no other sex differences. Birth-order analyses revealed minimal but significant differences in turning over from back to belly and for sitting without support between the first- and second-born. Dizygotic (DZ) twins were faster than monozygotic (MZ) twins in achieving the moment of sit, crawl, stand and walk. Twins born in earlier cohorts were faster in reaching the moment of crawl, sit and walk. It is concluded that there are no differences in time of reaching motor milestones between twins and singletons within the normal range. Sex has minimal to no effect on motor development in early childhood. DZ twins achieve motor milestones sooner than MZ twins. Attainment of gross motor milestones (crawl, stand and walk) is delayed in later birth cohorts.

AbstractThe present study assessed the prevalence of asthma and allergy, and estimated the importance of genetic and environmental influences on asthma and allergy liability and their association. Longitudinal data on self-reported, doctor-diagnosed asthma and allergy were collected in over 14,000 individuals registered with the Netherlands Twin Register. Structural equation modeling was used for univariate and bivariate genetic analyses on data from twins, their siblings, and parents. Results showed no sex, age, and minimal birth cohort effects for asthma prevalence (11.8%). For allergy, prevalence was higher in women (19.8%) than in men (13.9%). Allergy prevalence at ages 22, 23, and 24 years increased from the 1970 to the 1980 birth cohort. The prevalence of allergy, but not of asthma, was higher in nontwin siblings than in twins. No assortative mating was observed. High (broad-sense) heritabilities were found for asthma (75%) and allergy (66%), with evidence for nonadditive genetic effects in asthma. The association between asthma and allergy (correlation = .65) was largely due to common genes (70%). No sex differences in genetic architecture were found. In conclusion, the prevalence of allergy but not of asthma increased in recent years. Individual differences in the liability to asthma, allergy and their co-occurrence are for a large part accounted for by differences in genetic background. Nonadditive gene action is important, which may have consequences for gene hunting strategies.

Chorion type may significantly influence the prenatal environment of twins. This study explored the associations between chorion type and gestational age, birth weight, birth length, and the timing of emergence of the first primary tooth in two populations of twins, Australian and Dutch. Additionally, we investigated the relationship between chorion type and birth weight discordance (BWD) in order to determine whether a significant relationship existed between discordance in birth weight and discordance in the timing of emergence of the first primary tooth. The two study samples consisted of 409 Australian twin pairs and 301 Dutch twin pairs, all of European ancestry. Data were collected through a combination of questionnaires and recording charts administered to the parents and through linkage with biological databases. In the Australian sample, monozygotic monochorionic (MZMC) twins experienced the shortest mean gestation time (35 weeks), the lowest mean birth length (46 cm) and the lowest mean birth weight (2.3 kg) compared with other twin groups. For the same variables in the Dutch sample, these trends with MZMC twinning were not observed. Chorion type did not significantly affect the mean timing of emergence of the first primary tooth in either sample. Monochorionicity was found to be significantly associated with BWD in both samples, but there was a significant association between BWD in MZMC twin pairs and timing of emergence of the first primary tooth only in the Australian sample. Results from this study support previous findings that the timing of emergence of the first primary tooth is influenced strongly by genetic factors and is well protected from environmental disturbances.

AbstractHuman growth is a complex and poorly understood process. We studied the effect of genetic and environmental factors on height and body mass index (BMI, kg/m2) based on maternal reports at 3, 4, 5, 7, 10 and 12 years of age in a large longitudinal cohort of Dutch twins (7755 complete twin pairs at age 3). Several multivariate variance component models for twins were fitted to the data using the Mx statistical package. The first-born twin was taller until age 10 and heavier until age 12 than the second-born co-twin. Heritability estimates were high for height (a2 = .58–.91) and BMI (a2 = .31–.82), but common and unshared environmental factors were also important. The phenotypic correlations across the ages for height and BMI were mainly explained by correlated additive genetic factors (ra = .77–.96 for height and .43–.92 for BMI), but common (rc = .40–.84 and .09–.78, respectively) and specific environmental correlations (re = .50–.81 and .42–.80, respectively) were also significant. Additive genetic factors decreased with increasing age difference for both height and BMI. However, the full Cholesky model, which does not make any assumptions regarding the underlying genetic structure, had the best fit. High genetic correlations across the ages, especially for height, may help further molecular genetic studies of human growth. Environmental factors affecting height and BMI during growth period are also important, and further studies are needed to identify these factors and test whether they interact with genetic factors.

AbstractCauses of individual differences in happiness, as assessed with the Subjective Happiness Scale, are investigated in a large of sample twins and siblings from the Netherlands Twin Register. Over 12,000 twins and siblings, average age 24.7 years (range 12 to 88), took part in the study. A genetic model with an age by sex design was fitted to the data with structural equation modeling in Mx. The heritability of happiness was estimated at 22% for males and 41% in females. No effect of age was observed. To identify the genomic regions contributing to this heritability, a genome-wide linkage study for happiness was conducted in sibling pairs. A subsample of 1157 offspring from 441 families was genotyped with an average of 371 micro-satellite markers per individual. Phenotype and genotype data were analyzed in MERLIN with multipoint variance component linkage analysis and age and sex as covariates. A linkage signal (logarithm of odds score 2.73, empirical p value 0.095) was obtained at the end of the long arm of chromosome 19 for marker D19S254 at 110 cM. A second suggestive linkage peak was found at the short arm of chromosome 1 (LOD of 2.37) at 153 cM, marker D1S534 (empirical p value of .209). These two regions of interest are not overlapping with the regions found for contrasting phenotypes (such as depression, which is negatively associated with happiness). Further linkage and future association studies are warranted.

AbstractIn the late 1980s The Netherlands Twin Register (NTR) was established by recruiting young twins and multiples at birth and by approaching adolescent and young adult twins through city councils. The Adult NTR (ANTR) includes twins, their parents, siblings, spouses and their adult offspring. The number of participants in the ANTR who take part in survey and / or laboratory studies is over 22,000 subjects. A special group of participants consists of sisters who are mothers of twins. In the Young NTR (YNTR), data on more than 50,000 young twins have been collected. Currently we are extending the YNTR by including siblings of twins. Participants in YNTR and ANTR have been phenotyped every 2 to 3 years in longitudinal survey studies, since 1986 and 1991 for the YNTR and ANTR, respectively. The resulting large population-based datasets are used for genetic epidemiological studies and also, for example, to advance phenotyping through the development of new syndrome scales based on existing items from other inventories. New research developments further include brain imaging studies in selected and unselected groups, clinical assessment of psychopathology through interviews, and cross-referencing the NTR database to other national databases. A large biobank enterprise is ongoing in the ANTR in which blood and urine samples are collected for genotyping, expression analysis, and meta-bolomics studies. In this paper we give an update on the YNTR and ANTR phenotyping and on the ongoing ANTR biobank studies.

From childhood into adolescence, the child's brain undergoes considerable changes in both structure and function. Twin studies are of great value to explore to what extent genetic and environmental factors explain individual differences in brain development and cognition. In The Netherlands, we initiated a longitudinal study in which twins, their siblings and their parents are assessed at three year intervals. The participants were recruited from The Netherlands Twin Register (NTR) and at baseline consisted of 112 families, with 9-year-old twins and an older sibling. Three years later, 89 families returned for follow-up assessment. Data collection included psychometric IQ tests, a comprehensive neuropsychological testing protocol, and parental and self-ratings of behavioral and emotional problems. Physical maturation was measured through assessment of Tanner stages. Hormonal levels (cortisol, luteinizing hormone, follicle-stimulating hormone, testosterone, and estrogens) were assessed in urine and saliva. Brain scans were acquired using 1.5 Tesla Magnetic Resonance Imaging (MRI), which provided volumetric measures and measures of cortical thickness. Buccal swabs were collected for DNA isolation for future candidate gene and genome-wide analysis studies. This article gives an overview of the study and the main findings. Participants will return for a third assessment when the twins are around 16 years old. Longitudinal twin-sibling studies that map brain development and cognitive function at well-defined ages aid in the understanding of genetic influences on normative brain development.