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AbstractDifferences between early (within 30 days) and late (after 30 days) respondents in a survey study were analyzed in twins and siblings registered with the Netherlands Twin Register. We compared early and late respondents on personality traits, health, lifestyle, and demographic variables. The odds of being a late respondent were significantly higher for men (OR 1.14), alcohol use on a daily/weekly basis (OR 1.20), having a relationship (OR 1.40), higher score on experience seeking scale (OR 1.02), and criticizing the questionnaire as too long (OR 1.27). The odds of being a late respondent were significantly lower for nontwin subjects (OR 0.71), regular cycling (OR 0.83), and judging the questionnaire to be fun (OR 0.80). There were no significant interactions with sex. To examine to what extent early and late response is influenced by genetic factors, twin and sibling data of 5040 subjects were analyzed. The best model includes genetic factors (31%), shared environmental influences (36%), and unique environmental influences (43%) on variation in response time.

AbstractA threefold increase for testicular carcinoma has been reported in male dizygotic twins. In this comment we suggest the hypothesis that over-exposure to endogenously hypersecreted Follicle Stimulating Hormone (FSH) may underlie the pathogenesis. This is supported by several findings. 1) FSH hypersecretion in mothers of dizygotic twins is most likely an autosomal trait implicating the possibility of male offspring with the same hormone characteristic. 2) In testicular carcinoma higher levels of cyclin D2 are found. This is an FSH dependent stimulatory regulator of mitosis. 3) There is a marked similarity between geographical distribution in occurence of dizygotic twinning and testicular carcinoma. 4) Men undergoing surgery for testicular carcinoma have higher FSH concentrations and males with Down syndrome have higher FSH levels and are more at risk to develop testicular carcinoma. We suggest to study FSH secretion in males of familial dizygotic twins and furthermore the risk of developing testicular carcinoma in males with elevated FSH. These men with one testicle and/or with dysfunctioning Sertoli/Leydig cells.

AbstractThe aim of this study was to estimate the heritability of variation in testosterone levels in 12-year-old children, and to explore the overlap in genetic and environmental influences on circulating testosterone levels and androgen-dependent pubertal development. Midday salivary testosterone samples were collected on 2 consecutive days in a sample of 183 unselected twin pairs. Androgen-induced pubertal development was assessed using self-report Tanner scales of pubic hair development (boys and girls) and genital development (boys). A significant contribution of genetic effects to the variance in testosterone levels was found. Heritability was approximately 50% in both boys and girls. The remaining proportion of the variance in testosterone levels could be explained by nonshared environmental influences. The relatively high correlation between testosterone levels of opposite-sex dizygotic twins suggests that sex differences in genes influencing variation in testosterone levels have not yet developed in preand early puberty. Variance in pubertal development was explained by a large genetic component, moderate shared environmental influences, and a small nonshared environmental effect. Testosterone levels correlated moderately (r = .31) with pubertal development; the covariance between testosterone levels and pubertal development was entirely accounted for by genetic influences.

AbstractThe heritability of the degree of residential area urbanization in twins and their siblings in the Dutch population was examined. The postal code was known for 6879 twins and 2724 siblings registered with the Netherlands Twin Register and born between 1940 and 1983. Using data from Statistics Netherlands (Centraal Bureau voor de Statistiek, 2001), these postal codes could be related to residential area characteristics, including urbanization level. The degree of urbanization was assessed on a 5-point scale: very heavy, heavy, moderate, low and not urbanized. Genetic model-fitting was carried out in three age cohorts: young adults (born 1975 to 1983), adults (born 1965 to 1974) and older adults (born 1940 to1964). Twin and sibling resemblance in urbanization level was expressed in polychoric correlations. These correlations decreased from the youngest cohort (.66 to .86) to the oldest cohort (.20 to .58). In all 3 age cohorts, genetic factors did not contribute to familial resemblance. The influence of common environment decreased in importance from the young cohort (70% to 83%) to the old cohort (46% to 47%) and was lower in women than in men in all but the oldest age cohort. This study did not replicate Australian findings of a genetic contribution in the older cohorts; common environmental factors and, increasingly with age, unique environmental factors determine where the Dutch live. Future studies in European and other populations will reveal whether these results are specific to the Dutch population.

AbstractWe compare the power of two different approaches to detect passive genotype–environment (GE) covariance originating from cultural and genetic transmission operating simultaneously. In the traditional nuclear twin family (NTF) design, cultural transmission is estimated from the phenotypic covariance matrices of the mono- and dizygotic twins and their parents. Here, phenotyping is required in all family members. A more recent method is the transmitted–nontransmitted (T–NT) allele design, which exploits measured genetic variants in parents and offspring to test for effects of nontransmitted alleles from parents. This design requires two-generation genome-wide data and a powerful genome-wide association study (GWAS) for the phenotype in addition to phenotyping in offspring. We compared the power of both designs. Using exact data simulation, we demonstrate three points: how the power of the T–NT design depends on the predictive power of polygenic risk scores (PRSs); that when the NTF design can be applied, its power to detect cultural transmission and GE covariance is high relative to T–NT; and that, given effect sizes from contemporary GWAS, adding PRSs to the NTF design does not yield an appreciable increase in the power to detect cultural transmission. However, it may be difficult to collect phenotypes of parents and the possible importance of gene × age interaction, and secular generational effects can cause complications for many important phenotypes. The T–NT design avoids these complications.

In a recent GWAS of spontaneous dizygotic twinning, Mbarek et al. (The American Journal of Human Genetics, 2016, Vol 98, pp. 898–908) identified two SNPs, rs11031006 (near FSHB) and rs17293443 (in SMAD3). In the present note, we address the question how to present the results in terms of effect sizes in a manner that is comprehensible to the general audience (e.g., mothers of twins, readership of newspapers). We propose to avoid the standard effect sizes such as odds ratios and relative risk as these require some knowledge of probability theory. Rather, we convey the results in terms of the conditional probabilities, but expressed in natural language.

AbstractRecent findings of an association between anesthesia administration in the first three years of life and later learning disabilities have created concerns that anesthesia has neurotoxic effects on synaptogenesis, causing later learning problems. An alternative hypothesis is that those children who are likely to undergo surgery early in life have significant medical problems that are associated with a vulnerability to learning disabilities. These two hypotheses were evaluated in a monozygotic concordant–discordant twin design. Data on anesthesia administration and learning abilities and disabilities were available for 1,143 monozygotic twin pairs (56% female) from the Netherlands Twin Registry. Parents of the twins reported on anesthesia use before age 3 and again between ages 3 and 12 years. Near age 12, educational achievement and cognitive problems were assessed with standardized tests and teacher ratings. Results showed that twins who were exposed to anesthesia before age 3 had significantly lower educational achievement scores and significantly more cognitive problems than twins not exposed to anesthesia. However, there was one important exception: the unexposed co-twin from discordant pairs did not differ from their exposed co-twin. Thus, there is no evidence for a causal relationship between anesthesia administration and later learning-related outcomes in this sample. Rather, there is evidence for early anesthesia being a marker of an individual's vulnerability for later learning problems, regardless of their exposure to anesthesia.

Genotype by environment interaction in behavioral traits may be assessed by estimating the proportion of variance that is explained by genetic and environmental influencesconditionalon a measured moderating variable, such as a known environmental exposure. Behavioral traits of interest are often measured by questionnaires and analyzed as sum scores on the items. However, statistical results on genotype by environment interaction based on sum scores can be biased due to the properties of a scale. This article presents a method that makes it possible to analyze the actually observed (phenotypic) item data rather than a sum score by simultaneously estimating the genetic model and an item response theory (IRT) model. In the proposed model, the estimation of genotype by environment interaction is based on an alternative parametrization that is uniquely identified and therefore to be preferred over standard parametrizations. A simulation study shows good performance of our method compared to analyzing sum scores in terms of bias. Next, we analyzed data of 2,110 12-year-old Dutch twin pairs on mathematical ability. Genetic models were evaluated and genetic and environmental variance components estimated as a function of a family's socio-economic status (SES). Results suggested that common environmental influences are less important in creating individual differences in mathematical ability in families with a high SES than in creating individual differences in mathematical ability in twin pairs with a low or average SES.

AbstractCaffeine 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%).

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.