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Socio-environmental factors play an important role in adolescent well-being, but potential genetic contributions to these associations are rarely assessed. To address this gap in the literature, associations between well-being and family conflict and functioning, number of friends, friendship importance and satisfaction, and leisure time variables were studied in N = ~ 4700 twin pairs from the Netherlands Twin Register, us ing generalized estimating equations and twin-difference scores. When twin-difference scores indicated a role for genetic factors, we used bivariate genetic models to quantify genetic and environmental contributions to these associations. We identify significant associations between well-being and family functioning, family conflict, different leisure time activities, number of friends, and satisfaction with friendships. Additionally, we find evidence for large (73–91%) genetic influence on the associations between well-being and family conflict and functioning, leisure time sport/scouting clubs, and satisfaction with friendships. Finally, findings support the hypothesis of a causal association between well-being and family conflict and functioning. These findings have important implications for research into the social correlates of well-being in adolescence, as not taking genetic factors into account leads to overestimations of the influence of identified correlates and consequently to recommendations of these correlates as intervention targets. [ABSTRACT FROM AUTHOR]

Background: Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design.Methods: We conducted a cohort study in twins (7-12 years; 25 781 twins) from the Netherlands Twin Register (NTR) and a replication study in the Childhood and Adolescent Twin Study in Sweden (CATSS; 7946 9-year-old twins). Antibiotic use was recorded before age 2 years. Attention-deficit hyperactivity disorder and autism spectrum disorder were parent-reported in the Netherlands Twin Register and register-based in the Childhood and Adolescent Twin Study in Sweden.Results: Early-life antibiotic use was associated with increased risk of attention-deficit hyperactivity disorder development [pooled odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02-1.17] and autism spectrum disorder (pooled OR 1.15, 95% CI 1.06-1.25) in a case-control design. When restricting to monozygotic twin pairs discordant for the outcome, associations disappeared for both disorders in both cohorts (attention-deficit hyperactivity disorder OR 0.90, 95% CI 0.48-1.69 and OR 0.80, 95% CI 0.37-1.76, and autism spectrum disorder OR 0.66, 95% CI 0.38-1.16 and OR 0.29, 95% CI 0.02-4.50, respectively).Conclusions: Our findings suggest that the association between early-life antibiotic use and risk of attention-deficit hyperactivity and autism spectrum disorder may be confounded by shared familial environment and genetics. [ABSTRACT FROM AUTHOR]

Objective: To assess the additional value of fetal multiplanar (axial, coronal and sagittal) neurosonography and magnetic resonance imaging (MRI) to that of the standard axial ultrasound planes in diagnosing brain damage in fetuses at high risk.Methods: This was a prospective, multicenter, observational study. Women were eligible for participation if their fetus was at risk for acquired brain anomalies. Risk factors were congenital infection, alloimmune thrombocytopenia, fetal growth restriction, trauma during pregnancy, fetal hydrops, monochorionic twins and prior ultrasound finding suggestive of an acquired brain anomaly. Examinations of the fetal brain before birth comprised axial ultrasound and advanced neurosonography biweekly and MRI once. After birth, neonatal cranial ultrasound was performed at < 24 h and at term-equivalent age. Neonatal brain MRI was performed once at term-equivalent age. An expert panel blinded to medical information, including imaging findings by the other methods, evaluated the presence of periventricular echogenicity (PVE) changes, peri- and intraventricular hemorrhage (IVH) and changes in basal ganglia and/or thalami echogenicity (BGTE) on ultrasound, and the equivalent signal intensity (SI) changes on MRI. Conclusions on imaging findings were generated by consensus. The children were followed up with examinations for psychomotor development at 1 year of age, using the Touwen examination and Alberta Infant Motor Scale, and at 2 years of age using Bayley Scale of Infant Development-III (BSID-III) and behavioral, sensory profile and linguistic questionnaires; scores > 1 SD below the mean were considered suspicious for neurodevelopmental sequelae.Results: Fifty-six fetuses were examined, and in 39/56 fetuses, all fetal-imaging modalities were available. PVE/SI changes were observed in 6/39, 21/39 and 2/39 fetuses on axial ultrasound planes, multiplanar neurosonography and MRI, respectively. IVH was found in 3/39, 11/39 and 1/39 fetuses, and BGTE/SI changes in 0/39, 12/39 and 0/39 fetuses, respectively. Outcome was suspicious for neurodevelopmental sequelae in 13/46 infants at 1 year, and at 2 years, 41/41 children had scores within 1 SD of the mean on BSID-III and 20 had scores > 1 SD below the mean on the behavioral (5/38), sensory profile (17/37) and/or linguistic (6/39) questionnaires.Conclusions: In this cohort of fetuses at risk for brain damage, the severity of acquired brain anomalies was limited. Nevertheless, multiplanar neurosonography detected more fetal PVE changes, IVH and/or BGTE changes compared to the standard axial ultrasound planes and MRI. Fetal MRI did not demonstrate any anomalies that were not seen on neurosonography. Neurodevelopmental outcome at 2 years of age showed no or mild impairment in most cases. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Our current society is characterized by an increased availability of industrially processed foods with high salt, fat and sugar content. How is it that some people prefer these unhealthy foods while others prefer more healthy foods? It is suggested that both genetic and environmental factors play a role. The aim of this study was to (1) identify food preference clusters in the largest twin-family study into food preference to date and (2) determine the relative contribution of genetic and environmental factors to individual differences in food preference in the Netherlands. Principal component analysis was performed to identify the preference clusters by using data on food liking/disliking from 16,541 adult multiples and their family members. To estimate the heritability of food preference, the data of 7833 twins were used in structural equation models. We identified seven food preference clusters (Meat, Fish, Fruits, Vegetables, Savory snacks, Sweet snacks and Spices) and one cluster with Drinks. Broad-sense heritability (additive [A] + dominant [D] genetic factors) for these clusters varied between .36 and .60. Dominant genetic effects were found for the clusters Fruit, Fish (males only) and Spices. Quantitative sex differences were found for Meat, Fish and Savory snacks and Drinks. To conclude, our study convincingly showed that genetic factors play a significant role in food preference. A next important step is to identify these genes because genetic vulnerability for food preference is expected to be linked to actual food consumption and different diet-related disorders. [ABSTRACT FROM AUTHOR]

Loneliness is related to mental and somatic health outcomes, including borderline personality disorder. Here, we analyze the sources of variation that are responsible for the relationship between borderline personality features (including four dimensions, affective instability, identity disturbance, negative relationships, self-harm and a total score) and loneliness. Using genetically informative data from two large nonclinical samples of adult twin pairs from Australia and the Netherlands (N = 11,329), we estimate the phenotypic, genetic and environmental correlations between self-reported borderline personality features and loneliness. Individual differences in borderline personality and loneliness were best explained by additive genetic factors with heritability estimates h2 = 41% for the borderline personality total score and h2 = 36% for loneliness, with the remaining variation explained by environmental influences that were not shared by twins from the same pair. Genetic and environmental factors influencing borderline personality (total score and four subscales separately) were also partial causes of loneliness. The correlation between loneliness and the borderline personality total score was rph = .51. The genetic correlation was estimated at rg = .64 and the environmental correlation at re = .40. Our study suggests common etiological factors in loneliness and borderline personality features. [ABSTRACT FROM AUTHOR]

A literature review was carried out to identify pre and perinatal characteristics associated with variation in Apgar scores in population-based studies. The parameters identified in the literature search were included in the classical twin design study to estimate effects of pre and perinatal factors shared and nonshared by twins and to test for a contribution of genetic factors in 1- and 5-min Apgar scores in a large sample of Dutch monozygotic (MZ) and dizygotic (DZ) twins. The sample included MZ and DZ twins (N = 5181 pairs) recruited by the Netherlands Twin Register shortly after birth, with data on prenatal characteristics and Apgar scores at first and/or fifth minutes. The ordinal regression and structural equation modeling were used to analyze the effects of characteristics identified in the literature review and to estimate genetic and nongenetic variance components. The literature review identified 63 papers. Consistent with the review, we observed statistically significant effects of birth order, zygosity and gestational age (GA) for 1- and 5-min Apgar scores of both twins. Apgar scores are higher in first-born versus second-born twins and DZ first-born versus MZ first-born twins. Birth weight had an effect on the 5-min Apgar of the first born. Fetal presentation and mode of delivery had different effects on Apgar scores of first- and second-born twins. Parental characteristics and chorionicity did not have significant main effects on Apgar scores. The MZ twins' Apgar correlations equaled the DZ Apgar correlations. Our analyses suggest that individual differences in 1- and 5-min Apgar scores are attributable to shared and nonshared pre and perinatal factors, but not to genotypic factors of the newborns. The main predictors of Apgar scores are birth order, zygosity, GA, birth weight, mode of delivery and fetal presentation. [ABSTRACT FROM AUTHOR]

Introduction: The common genetic variant (rs1051730) in the 15q24 nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 was associated with smoking quantity and has been reported to be associated also with reduced ability to quit smoking in pregnant women but results were inconsistent in nonpregnant women. The aim of this study was to explore the association between rs1051730 and smoking cessation during pregnancy in a sample of Dutch women.Methods: Data on smoking during pregnancy were available from 1337 women, who ever smoked, registered at the Netherlands Twin Register (NTR). Logistic regression was used to assess evidence for the association of rs1051730 genotype on smoking during pregnancy. In a subsample of 561 women, we investigated the influence of partner's smoking. Educational attainment and year of birth were used as covariates in both analyses.Results: There was evidence for a significant association between having one or more T alleles of the rs1051730 polymorphism and the likelihood of smoking during pregnancy (p = .03, odds ratio = 1.28, 95% CI = 1.02 to 1.61). However, this association attenuated when adjusting for birth cohort and educational attainment (p = .37, odds ratio = 1.12, 95% CI = 0.87 to 1.43). In the subsample, smoking spouse was highly associated with smoking during pregnancy, even when educational attainment and birth cohort were included in the model.Conclusions: Our results did not support a strong association between this genetic variant and smoking during pregnancy. However, a strong association was observed with the smoking behavior of the partner, regardless of the genotype of the women.Implications: The present study emphasizes the importance of social influences like spousal smoking on the smoking behavior of pregnant women. Further research is needed to address the role of rs1051730 genetic variant in influencing smoking cessation and the interaction with important environmental factors like the smoking behavior of the partner. [ABSTRACT FROM AUTHOR]

Objective: To compare, in women with twin pregnancy with the first twin in cephalic position, neonatal morbidity and mortality rates after planned caesarean delivery (CD) versus planned vaginal delivery (VD).Study Design: A nationwide cohort study on women pregnant with twins and the first child in cephalic position, who delivered between 32 + 0-41 + 0 weeks between 2000 and 2012 in the Netherlands, using multivariate logistic regression analysis to compare neonatal morbidity and mortality according to planned delivery mode, and looking at subgroups 32 + 0-36 + 6 and 37 + 0-41 + 0 weeks.Results: We included 21,107 women, of whom 1384 (6.6%) had a planned CD. Of the 19,723 women (93.4%) who had a planned VD, 19.7% delivered by intrapartum CD. We found no significant differences in 'any mortality' (aOR planned CD vs. planned VD 1.34 (95% CI 0.63-2.60)), the outcome 'Apgar score (AS) < 4 or death within 28 days' (aOR 1.28 (95% CI 0.77-2.11) or asphyxia-related morbidity (aOR 0.57 (95% CI 0.32-1.03)). After planned CD more prematurity-related morbidity (aOR 1.55 (95% CI 1.21-1.98)), other morbidity (aOR 1.50 (95% CI 1.26-1.78)) and 'any morbidity or mortality' (aOR 1.41 (95% CI 1.20-1.66) was noted. Trauma-associated morbidity was absent after planned CD and occurred 45 times (0.2%) after planned VD. Before 36 + 6 weeks, planned CD resulted in more perinatal mortality (aOR 2.10 (95% CI 0.92-4.76)), while asphyxia-related morbidity did not differ (aOR 0.80 (95% CI 0.41-1.54). Planned CD resulted in more 'any morbidity or mortality' (aOR 1.52 (95% CI 1.25-1.84)), 'AS < 4 or death within 28 days' (aOR 1.77 (95% CI 1.02-3.09)), prematurity-related morbidity (aOR 1.73 (95% CI 1.34-2.23)), and 'other morbidity' (aOR 1.56 (95% CI 1.28-1.90)). After 37 weeks, no significance differences in mortality, 'any morbidity or mortality <28 days' (aOR 0.96 (95% CI 1 (0.67-1.38)), or 'AS < 4 or death within 28 days' (aOR 0.41 (95% CI (0.10-1.70)) were found. There was less asphyxia-related morbidity after planned CD (aOR 0.24 (95% CI 0.06-1.002)).Conclusion: Planned VD results in comparable neonatal outcomes as planned CD for twin pregnancy with the first twin in cephalic position, even with a low intrapartum CD rate of 19.7%. At term, a planned CD may result in less asphyxia- and trauma-related outcomes. [ABSTRACT FROM AUTHOR]

Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. [ABSTRACT FROM AUTHOR]

Over the past decades, Internet use has grown substantially, and it now serves people as a supportive tool that is used regularly and-in large parts of the world-inevitably. Some people develop problematic Internet use, which may lead to addictive behavior and it is becoming important to explore the risk factors for compulsive Internet use. Data were analyzed on compulsive Internet use [with the Compulsive Internet Use Scale (CIUS)] from 5247 monozygotic (MZ) and dizygotic (DZ) adolescent twins registered with the Netherlands Twin Register. The participants form a sample that is informative for genetic analyses, allowing the investigation of the causes of individual differences in compulsive Internet use. The internal consistency of the instrument was high and the 1.6-year test-retest correlation in a subsample (n = 902) was 0.55. CIUS scores increased slightly with age. Remarkably, gender did not explain variation in CIUS scores, as mean scores on the CIUS were the same in boys and girls. However, the time spent on specific Internet activities differed: boys spent more time on gaming, whereas girls spent more time on social network sites and chatting. The heritability estimates were the same for boys and girls: 48 percent of the individual differences in CIUS score were influenced by genetic factors. The remaining variance (52 percent) was due to environmental influences that were not shared between family members. Because a life without Internet is almost impossible nowadays, it is important to further explore the determinants of compulsive Internet use, including genetic risk factors. [ABSTRACT FROM AUTHOR]

Objective: To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section.Methods: This was a secondary analysis of two randomized trials conducted in 57 hospitals in The Netherlands. We assessed the univariable association between risk indicators, including second-trimester CL in quartiles, and emergency Cesarean delivery using a logistic regression model. For multivariable analysis, we assessed whether adjustment for other risk indicators altered the associations found in univariable (unadjusted) analysis. Separate analyses were performed for suspected fetal distress and failure to progress in labor as indications for Cesarean section.Results: In total, 311 women with a twin pregnancy attempted vaginal delivery after 34 weeks' gestation. Emergency Cesarean delivery was performed in 111 (36%) women, of which 67 (60%) were performed owing to arrest of labor. There was no relationship between second-trimester CL and Cesarean delivery (adjusted odds ratio (aOR): 0.97 for CL 26(th) -50(th) percentiles; 0.71 for CL 51(st)  - 75(th) percentiles; and 0.92 for CL > 75(th) percentile, using CL ≤ 25(th) percentile as reference). In multivariable analysis, the only variables associated with emergency Cesarean delivery were maternal age (aOR, 1.07 (95% CI, 1.00-1.13)), body mass index (BMI) (aOR, 3.99 (95% CI, 1.07-14.9) for BMI 20-23 kg/m(2) ; 5.04 (95% CI, 1.34-19.03) for BMI 24-28 kg/m(2) ; and 3.1 (95% CI, 0.65-14.78) for BMI > 28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5)).Conclusion: In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery. [ABSTRACT FROM AUTHOR]

In order to estimate the influence of genetic and environmental factors on 'crying without a cause' and 'being easily upset' in 2-year-old children, a large twin study was carried out. Prospective data were available for ~18,000 2-year-old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis was performed using structural equation modeling in the Mx software package. The influence of maternal personality characteristics and demographic and lifestyle factors was tested to identify specific risk factors that may underlie the shared environment of twins. Furthermore, it was tested whether crying without a cause and being easily upset were predictive of later internalizing, externalizing and attention problems. Crying without a cause yielded a heritability estimate of 60% in boys and girls. For easily upset, the heritability was estimated at 43% in boys and 31% in girls. The variance explained by shared environment varied between 35% and 63%. The correlation between crying without a cause and easily upset (r = .36) was explained both by genetic and shared environmental factors. Birth cohort, gestational age, socioeconomic status, parental age, parental smoking behavior and alcohol use during pregnancy did not explain the shared environmental component. Neuroticism of the mother explained a small proportion of the additive genetic, but not of the shared environmental effects for easily upset. Crying without a cause and being easily upset at age 2 were predictive of internalizing, externalizing and attention problems at age 7, with effect sizes of .28-.42. A large influence of shared environmental factors on crying without a cause and easily upset was detected. Although these effects could be specific to these items, we could not explain them by personality characteristics of the mother or by demographic and lifestyle factors, and we recognize that these effects may reflect other maternal characteristics. A substantial influence of genetic factors was found for the two items, which are predictive of later behavioral problems. [ABSTRACT FROM AUTHOR]

We assessed the heritability of head circumference, an approximation of brain size, in twin-sib families of different ages. Data from the youngest participants were collected a few weeks after birth and from the oldest participants around age 50 years. In nearly all age groups the largest part of the variation in head circumference was explained by genetic differences. Heritability estimates were 90% in young infants (4 to 5 months), 85-88% in early childhood, 83-87% in adolescence, 75% in young and mid adulthood. In infants younger than 3 months, heritability was very low or absent. Quantitative sex differences in heritability were observed in 15- and 18-year-olds, but there was no evidence for qualitative sex differences, that is, the same genes were expressed in both males and females. Longitudinal analysis of the data between 5, 7, and 18 years of age showed high genetic stability (.78 > R(G) > .98). These results indicate that head circumference is a highly heritable biometric trait and a valid target for future GWA studies. [ABSTRACT FROM AUTHOR]

Background: The tendency to conceive dizygotic (DZ) twins is a complex trait influenced by genetic and environmental factors. To search for new candidate loci for twinning, we conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism marker panels.Methods and Results: Non-parametric linkage analyses, including 523 families containing a total of 1115 mothers of DZ twins (MODZT) from Australia and New Zealand (ANZ) and The Netherlands (NL), produced four linkage peaks above the threshold for suggestive linkage, including a highly suggestive peak at the extreme telomeric end of chromosome 6 with an exponential logarithm of odds [(exp)LOD] score of 2.813 (P = 0.0002). Since the DZ twinning rate increases steeply with maternal age independent of genetic effects, we also investigated linkage including only families where at least one MODZT gave birth to her first set of twins before the age of 30. These analyses produced a maximum expLOD score of 2.718 (P = 0.0002), largely due to linkage signal from the ANZ cohort, however, ordered subset analyses indicated this result is most likely a chance finding in the combined dataset. Linkage analyses were also performed for two large DZ twinning families from the USA, one of which produced a peak on chromosome 2 in the region of two potential candidate genes. Sequencing of FSHR and FIGLA, along with INHBB in MODZTs from two large NL families with family specific linkage peaks directly over this gene, revealed a potentially functional variant in the 5' untranslated region of FSHR that segregated with the DZ twinning phenotype in the Utah family.Conclusion: Our data provide further evidence for complex inheritance of familial DZ twinning. [ABSTRACT FROM AUTHOR]

Causes 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. [ABSTRACT FROM AUTHOR]

Research on twin-singleton differences in externalizing and internalizing problems in childhood is largely cross-sectional and yields contrasting results. The goal of this study was to compare developmental trajectories of externalizing and internalizing problems in 6- to 12-year-old twins and singletons. Child Behavior Checklist (CBCL) maternal reports of externalizing and internalizing problems were obtained for a sample of 9651 twins from the Netherlands Twin Register and for a representative general population sample of 1351 singletons. Latent growth modeling was applied to estimate growth curves for twins and singletons. Twin-singleton differences in the intercepts and slopes of the growth curves were examined. The developmental trajectories of externalizing problems showed a linear decrease over time, and were not significantly different for twins and singletons. Internalizing problems seem to develop similarly for twins and singletons up to age 9. After this age twins' internalizing symptoms start to decrease in comparison to those of singletons, resulting in less internalizing problems than singletons by the age of 12 years. Our findings confirm the generalizability of twin studies to singleton populations with regard to externalizing problems in middle and late childhood. The generalizability of studies on internalizing problems in early adolescence in twin samples should be addressed with care. Twinship may be a protective factor in the development of internalizing problems during early adolescence. [ABSTRACT FROM AUTHOR]

The contribution of genetic and environmental factors to the stability of obsessive-compulsive (OC) symptoms has not yet been established in adult population based samples. We obtained the Young Adult Self Report Obsessive-Compulsive Subscale in mono- and dizygotic twins from the population-based Netherlands Twin Register in 1991, 1995 and 1997 and the Padua Inventory Revised Abbreviated in 2002. Stability of OC symptoms was analyzed as a function of genetic and environmental components. Heritability of OC behavior was around 40% at each time-point, independent of the instrument used. OC behavior was moderately stable with correlations ranging between r = .2 (for 11-year intervals), .4 (for 4-5 year intervals) and .6 (for 2 year intervals). Genetic correlations across time were higher, varying between .4 and .9, indicating that the stability of OC symptoms is mainly due to stable genetic factors. This study showed a moderate heritability and stability for OC behavior in adults. Genetic stability across time is high. [ABSTRACT FROM AUTHOR]

Caffeine is by far the most commonly used psychoactive substance. Caffeine is consumed regularly as an ingredient of coffee. Coffee consumption and coffee preference was explored in a sample of 4,495 twins (including 1,231 pairs) registered with the Netherlands Twin Registry. Twin resemblance was assessed by tetrachoric correlations and the influence of both genetic and environmental factors was explored with model fitting analysis in MX. Results showed moderate genetic influences (39%) on coffee consumption. The remaining variance was explained by shared environmental factors (21%) and unique environmental factors (40%). The variance in coffee preference (defined as the proportion of coffee consumption relative to the consumption of coffee and tea in total) was explained by genetic factors (62%) and unique environmental factors (38%). [ABSTRACT FROM AUTHOR]

Human height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1,521] polymorphisms). We genotyped large Caucasian samples from Australia (N = 3,906) and the Netherlands (N = 1,689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3 cm) to the effect observed in the published adult meta-analysis. An effect of this size explains approximately 0.1% of the phenotypic variance in height - this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height. [ABSTRACT FROM AUTHOR]

A 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. [ABSTRACT FROM AUTHOR]

Several 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. [ABSTRACT FROM AUTHOR]

Our 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. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the reliability of obtaining through mailed surveys maternal reports of specific major motor milestones achievement. To accomplish this aim we compared and contrasted mailed survey data and telephone interview data on a series of questions about age at which motor milestones were achieved. We used monthly telephone interviews with mothers of 238 twin pairs, beginning at age 6 months, which ascertained the age at which each specific milestone was met. The contrasting 'through the mail' survey was sent after the second birthday of an independent group of children, and included 463 twin pairs. All twins were born between March 2003 and March 2004. Comparisons were made for the following 5 milestones: sitting without support, hands and knees crawling, turning from back to belly, standing without support, and walking without support. There was no difference between the concurrent telephone interviews and the retrospective through the mail survey on any of the landmarks, except 'standing without support'. From this work we conclude that data on achieving milestones can be reliably obtained through the mail using retrospective surveys when the children are 2 years of age. [ABSTRACT FROM AUTHOR]

A high body mass index (BMI) is commonly used as an index of overweight and obesity. There is persistent evidence of high heritability for variation in BMI, but the effects of common environment appear inconsistent across different European countries. Our objective was to compare genetic and environmental effects on BMI in a sample of twins from two different European countries with distinct population and cultural backgrounds. We analysed data of adult female twins from the Netherlands Twin Register (222 monozygotic [MZ] and 103 dizygotic [DZ] pairs) and the Murcia Twin Register (Spain; 202 MZ and 235 DZ pairs). BMI was based on self-reported weight and height. Dutch women were taller and heavier, but Spanish women had a significantly higher mean BMI. The age related weight increase was significantly stronger in the Spanish sample. Genetic analyses showed that genetic factors are the main contributors to variation in height, weight, and BMI, within both countries. For height and weight, estimates of genetic variances did not differ, but for height, the estimate for the environmental variance was significantly larger in Spanish women. For BMI, both the genetic and the environmental variance components were larger in Spanish than in Dutch women. [ABSTRACT FROM AUTHOR]

This article analyzes the effect of classroom separation of twins on their cognitive abilities, measured at different ages in Dutch primary education. We use a large longitudinal school-based sample of twins and their classmates. The analysis tries to reduce the bias by unobserved factors due to the nonrandom assignment of twins by taking into account differences in school environment, previous test scores and variation in class assignment between years. We find that classroom separation matters for language in Grade 2. Nonseparated twins score higher on language, and the difference is larger for same-sex pairs. This finding is robust for various methods that take unobserved effects into account. In addition, there is some evidence for higher scores in arithmetic in Grade 2. For the higher grades we find no effect of classroom separation on cognitive ability. In the analysis of the effect of a separation of at least 3 years we find that separation increases language performance between Grade 6 and 8 for opposite-sex pairs. [ABSTRACT FROM AUTHOR]

The effect of nonresponse on health and lifestyle measures has received extensive study, showing at most relatively modest effects. Nonresponse bias with respect to personality has been less thoroughly investigated. The present study uses data from responding individuals as a proxy for the missing data of their nonresponding family members to examine the presence of nonresponse bias for personality traits and disorders as well as health and lifestyle traits. We looked at the Big Five personality traits, borderline personality disorder (BPD) features, attention-deficit/hyperactivity disorder, Anger, and several measures of health (Body Mass Index, migraine) and lifestyle (smoking, alcohol use). In general, outcomes tend to be slightly more favorable for individuals from highly cooperative families compared to individuals from less cooperative families. The only significant difference was found for BPD features (p = .001). However, the absolute difference in mean scores is very small, less than 1 point for a scale ranging from 0 to 72. In conclusion, survey data on personality, health and lifestyle are relatively unbiased with respect to nonresponse. [ABSTRACT FROM AUTHOR]

Human 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/m(2)) 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 (a(2) = .58-.91) and BMI (a(2) = .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 (r(a) = .77-.96 for height and .43-.92 for BMI), but common (r(c) = .40-.84 and .09-.78, respectively) and specific environmental correlations (r(e) = .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. [ABSTRACT FROM AUTHOR]

Evidence for a relation between neuroticism and religion is scarce and inconsistent. The aims of the present study were to determine the association of religious upbringing with adult neuroticism scores and to examine the effect of religious upbringing on the heritability of neuroticism. As part of a longitudinal survey of twin families from the Netherlands Twin Register, data were collected on neuroticism and religious upbringing. Restricting the sample to persons aged 25 and over resulted in a sample of 4369 twins and 1304 siblings from 2698 families. Religious upbringing was significantly associated with neuroticism; in both men and women neuroticism levels were lower in those who had received a religious upbringing. There were no sex or twin sibling differences in neuroticism variances and covariances. Structural equation modeling showed differences in heritability between those with and without religious upbringing. In the group with religious upbringing, variation in neuroticism was determined for 41% by additive genetic factors and for the remaining 59% by unique environmental factors. In the group who had not received a religious upbringing, variation in neuroticism was determined for 55% by genetic factors, with evidence for both additive and nonadditive factors, and for the remaining 45% by unique environmental influences. In conclusion, having received a religious upbringing is associated with lower neuroticism scores and a lower heritability in adulthood. [ABSTRACT FROM AUTHOR]

Previous studies in young and adolescent twins suggested substantial genetic contributions to the amplitude and latency of the P3 evoked by targets in an oddball paradigm. Here we examined whether these findings can be generalized to adult samples. A total of 651 twins and siblings from 292 families participated in a visual oddball task. In half of the subjects the age centered around 26 (young adult cohort), in the other half the age centered around 49 (middle-aged adult cohort). P3 peak amplitude and latency were scored for 3 midline leads Pz, Cz, and Fz. No cohort differences in heritability were found. P3 amplitude (approximately 50%) and latency (approximately 45%) were moderately heritable for the 3 leads. A single genetic factor influenced latency at all electrodes, suggesting a single P3 timing mechanism. Specific genetic factors influenced amplitude at each lead, suggesting local modulation of the P3 once triggered. Genetic analysis of the full event-related potential waveform showed that P3 heritability barely changes from about 100 ms before to 100 ms after the peak. Age differences are restricted to differences in means and variances, but the proportion of genetic variance as part of the total variance of midline P3 amplitude and latency does not change from young to middle-aged adulthood. [ABSTRACT FROM AUTHOR]

In previous studies we obtained evidence that variation in loneliness has a genetic component. Based on adult twin data, the heritability estimate for loneliness, which was assessed as an ordinal trait, was 48%. These analyses were done on loneliness scores averaged over items ('I feel lonely' and 'Nobody loves me') and over time points. In this article we present a longitudinal analysis of loneliness data assessed in 5 surveys (1991 through 2002) in Dutch twins (N = 8389) for the two separate items of the loneliness scale. From the longitudinal growth modeling it was found sufficient to have non-zero variance for the intercept only, while the other effects (linear, quadratic and cubic slope) had zero variance. For the item 'I feel lonely' we observed an increasing age trend up to age 30, followed by a decline to age 50. Heritability for individual differences in the intercept was estimated at 77%. For the item 'Nobody loves me' no significant trend over age was seen; the heritability of the intercept was estimated at 70%. [ABSTRACT FROM AUTHOR]

The Netherlands Twin Register (NTR) was established around 1987 at the Vrije Universiteit in Amsterdam, the Netherlands. The current article summarizes the longitudinal genetic analyses of maternal and paternal ratings of twins' behavior as a function of the sex of the children for the traits of aggression (AGG), attention problems (AP), anxious/depression (ANX), internalizing behavior (INT) and externalizing behavior (EXT). We found that genetic influences are the most important factor in explaining individual differences in these traits. For most phenotypes, influences of genetic factors fluctuate throughout development, with the exception of AP, for which genetic influences remain of similar magnitude. Changes in genetic influences parallel those in shared environmental influences, while nonshared environmental influences remain relatively constant. Around 10% to 20% of the variance is accounted for by parent-specific shared environment, which includes rater bias. For all phenotypes, stability throughout childhood is accounted for by genetic and shared environmental factors, while nonshared environmental influences are mainly age/measurement specific. About 15% of the phenotypic stability is accounted for by rater-specific shared environmental influences, which include rater bias. In conclusion, between ages 3 and 12 genetic factors are the most important cause of individual differences in emotional and behavioral problems. [ABSTRACT FROM AUTHOR]

In 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 metabolomics studies. In this paper we give an update on the YNTR and ANTR phenotyping and on the ongoing ANTR biobank studies. [ABSTRACT FROM AUTHOR]

Background: Folate metabolism is critical to embryonic development, influencing neural tube defects (NTD) and recurrent early pregnancy loss. Polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) have been associated with dizygotic (DZ) twinning through pregnancy loss.Methods: The C677T and A1298C polymorphisms in MTHFR were genotyped in 258 Australasian families (1016 individuals) and 118 Dutch families (462 individuals) of mothers of DZ twins and a population sample of 462 adolescent twin families (1861 individuals). Haplotypes were constructed from the alleles, and transmission of the MTHFR haplotypes to mothers of DZ twins and from parents to twins in the adolescent twin families analysed.Results: The C677T and A1298C were common in all three populations (frequencies > 0.29). There was strong linkage disequilibrium (D' = 1) between the variants, showing that specific combinations of alleles (haplotypes) were transmitted together. Three haplotypes accounted for nearly all the variation. There was no evidence of any association between MTHFR genotype and twinning in mothers of twins, or of the loss of specific MTHFR genotypes during twin pregnancies.Conclusions: It is concluded that variation in twinning frequency is not associated with MTHFR genotype. [ABSTRACT FROM AUTHOR]