Netherlands Twin Register: a focus on longitudinal research.

In 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a few weeks or months after birth. Currently we register around 50% of all newborn multiples in The Netherlands. Their parents receive a questionnaire at registration and afterwards when the children are 2, 3, 5, 7, 10 and 12 years of age. Teachers are asked to rate the behavior of the children at ages 7, 10 and 12 years. Adolescent and young-adult twins were recruited through City Councils in the early 1990s. These twins, their parents and siblings participate in longitudinal survey studies that include items about health, fertility, lifestyle, addiction, personality and psychopathology, religion, socioeconomic status, and educational attainment. The total number of twins and multiples registered with the NTR is currently over 60,000. Subgroups of twins and siblings take part in studies of cognitive development, brain function and neuropsychological indices of attention processes, and molecular genetic studies of classical and behavioral cardiovascular risk factors. DNA samples are currently collected in selected twin families for two large linkage studies, which aim to find QTLs for anxious depression and for nicotine addiction. Sisters who are mothers of DZ twins contribute DNA samples for a linkage study of DZ twinning. Large cohorts of phenotyped family members from the general population are very valuable for genetic epidemiological studies and permit selection of informative families for gene finding studies.     

Netherlands twin family study of anxious depression (NETSAD).

In a longitudinal study of Dutch adolescent and young adult twins, their parents and their siblings, questionnaire data were collected on depression, anxiety and correlated personality traits, such as neuroticism. Data were collected by mailed surveys in 1991, 1993, 1995 and 1997. A total of 13,717 individuals from 3344 families were included in the study. To localise quantitative trait loci (QTLs) involved in anxiety and depression, the survey data were used to select the most informative families for a genome-wide search. For each individual a genetic factor score was computed, based on a genetic multivariate analysis of anxiety, depression, neuroticism and somatic anxiety. A family was selected if at least two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low) and concordant (high-high and low-low) pairs were included in the selected sample. Once an extreme sibling pair was selected, all family members (parents and additional siblings of the selected pair) who had at least once returned a questionnaire booklet were asked to provide a DNA sample. In total, 2724 individuals from 563 families (1007 parents and 1717 offspring) were approached and 1975 individuals from 479 families (643 patients and 1332 offspring) complied by returning a buccal swab for DNA isolation. All offspring from selected families were asked to participate in a psychiatric interview and in a 24-hour ambulatory assessment of cardiovascular parameters and cortisol. The interview consisted of the WHO-Composite International Diagnostic Interview and was administered to 1253 offspring. In this paper we describe the genetic-epidemiological analyses of the survey data on anxiety, somatic anxiety, neuroticism and depression. We detail how these data were used to select families for the QTL study and discuss strategies that may help elucidate the molecular pathways leading from genes to anxious depression.     

Protease inhibitor (Pi) locus,fertility and twinning

Summary In a sample of 160 Dutch twin pairs and their parents, we found that mothers of dizygotic twins had frequencies of the S and Z alleles at the protease inhibitor (Pi) locus that were 3 times higher than a control sample. Mothers of identical twins also had a higher frequency of S than controls. The S allele may thus both increase ovulation rate and enhance the success of multiple pregnancies. There was also an increased frequency of the S allele in fathers of dizygotic twins; however, this may be a secondary effect of assortative mating for family size (indicating by the number of siblings of the parents), for which a correlation of 0.2 was observed. Parents of dizygotic twins came from larger families than parents of monozygotic twins, but no effect of Pi type on family size was seen.     

Genetic and Familial Environmental Effects on Suicide – An Adoption Study of Siblings

Background

While there is clear evidence of familial influences on suicide, the origin of these is less certain. We have investigated genetic and familial environmental factors by studying the occurrence of suicide in biological and adoptive siblings of adoptees who died by suicide compared to siblings of surviving adoptees.

Method

We used the Danish Adoption Register and Danish population registers to compare 221 siblings of adoptees who died by suicide with the siblings of 1,903 adoptees who did not die by suicide. All adoptions in the Danish Adoption Register are non-familial, i.e. the adoptive parents are biologically unrelated to the adoptee. Analyses were conducted on incidence rates of suicide in biological and adoptive siblings given occurrence of suicide in the adoptees while also taking into account psychiatric disorders.

Results

The risk of suicide in full siblings of adoptees who died by suicide before age 60 years was significantly higher than in full siblings of adoptees who had not died by suicide (incidence rate ratios (IRR) = 5.01; 95% confidence interval [CI] = 1.28 - 19.6). This increase persisted after adjustment for history of psychiatric admission of siblings (IRR = 4.19; 95% CI = 1.00 - 17.5).

Conclusions

Genetic factors influence risk of suicide, probably independently of psychiatric disorder. This is relevant in provision of advice to families, including possible prevention of suicide.     

Twins and non-twin siblings: different estimates of shared environmental influence in early childhood.

Twin studies typically indicate shared environmental influence for cognitive abilities, especially in early childhood. However, across studies, DZ twin correlations tend to be greater than non-twin sibling correlations, suggesting that twin estimates of shared environment are to some extent specific to twins. We tested this hypothesis in a sample of more than 1800 MZ and 1800 same-sex DZ pairs from the Twins Early Development Study (TEDS), a study of twins born in England and Wales in 1994 and 1995. For this analysis, we obtained comparable data from more than 130 same-sex younger siblings of the twins. Twins and their younger siblings were assessed for language, cognitive abilities and behavior problems by their parents at 2 and 3 years of age. For language and cognitive measures at both 2 and 3 years, but not for behavior problems, estimates of shared environment were more than twice as large for twins as compared to non-twin siblings. We conclude that about half of twin study estimates of shared environment for cognitive abilities in early childhood are specific to twins. Although many possibilities exist for explaining the special shared environment effect for twins, we suggest that cognitive-relevant experiences that are not shared by siblings are shared by twins because they are exactly the same age.     

Role of various factors in determination of mono- and dizygotic twinning in man]

The multifactorial correlative analysis of the effect of certain factors influencing the appearance of either DZ or MZ twins in 259 families with known twins in them was carried out. It is shown that the probability of MZ twins birth in a family increases with mother's height growing, relations between parents getting worse and also in families where mother does physical work, while a probability of DZ twins birth depends on mother using contraceptives, increases in families with better nutrition and with father's age growing.     

Differential parental investment in families with both adopted and genetic children

Stepchildren are abused, neglected and murdered at higher rates than those who live with two genetically related parents. Daly and Wilson used kin selection theory to explain this finding and labeled the phenomenon “discriminative parental solicitude.” I examined discriminative parental solicitude in American households composed of both genetic and unrelated adopted children. In these families, kin selection predicts parents should favor their genetic children over adoptees. Rather than looking at cases of abuse, neglect, homicide and other antisocial behavior, I focused on the positive investments parents made in their children as well as the outcomes of each child. The results show that parents invested more in adopted children than in genetically related ones, especially in educational and personal areas. At the same time, adoptees experienced more negative outcomes. They were more likely to have been arrested, to have been on public assistance and to require treatment for drug, alcohol or mental health issues. They also completed fewer years of schooling and were more likely to divorce. In adoptive families, it appears that “the squeaky wheel gets the grease.” Parents invest more in adoptees not because they favor them, but because they are more likely than genetic children to need the help. I conclude that discriminative parental solicitude differs in adoptive and step households because adoptive families generally result from prolonged parenting effort, not mating effort like stepfamilies.     

Factors in the rejection and survival of captive cotton top tamarins (Saguinus oedipus)

Captive colonies of cotton top tamarins experience a high rate of rejection of infants within the 1st week of life. The rates of rejection and survival to maturity (2 or more years) among 659 live colony-born infants were correlated with rearing, birth group, litter size, season of birth, gender, origin of parents, experience of parents raising siblings, parity and age of parents, and experience of parent pairs. The most important factors associated with low rejection rates were family life and parental experience raising infants. Infants born into family groups or reared in families were rejected at a significantly lower rate. Rejection of infants whose sires were raised with siblings was significantly lower. Paternal experience was more important than maternal experience. Litter size had no effect on rejection of infants born to family groups, whereas, rejection of triplets was significantly higher than twins or singles among those born to parents alone. Rejection was significantly higher among primiparous births than multiparous birth. The combined experience of colony-born parents was not related to rejection if there were no sibling helpers in the cage at the time of birth. Rejection was significantly lower if sibling helpers were present. High survival of infants who were not rejected was correlated with rearing by or being born into family groups and higher parity and older age of the sires.     

Seoul Twin Family Study: design, sampling, assessments, and future directions.

The Seoul Twin Family Study seeks to investigate genetic and environmental influences on the development of cognitive abilities and other psychological traits among children and adolescents in Seoul, South Korea. In November, 2001 with the assistance of the Seoul Metropolitan Office of Education, we began to solicit all private and public schools in Seoul to obtain names, addresses, and telephone numbers of the twins enrolled in schools in Seoul. The vast majority of the recruited twins were between 6 and 18 years old. The recruited twins and their non-twin siblings and parents will undergo comprehensive assessment of cognitive abilities, interests, daily activities, personality, and familial and non-familial environments. We plan to reassess the twins and their families every two years as the twins progress through major changes that characterize childhood, adolescence, and adulthood. In addition, medical records of the twins during the prenatal period will be examined to determine the effects of intrauterine environment on individual differences in cognitive abilities and other psychological traits. We also plan to undertake molecular genetic studies to identify genes involved in specific cognitive abilities.     

Transracial adoption: white American adoptive mothers’ constructions of social capital in raising their adopted children

In the field of adoption and child welfare, there is ongoing debate and discussion about how white adoptive parents in transracial families construct personal and social relationships and networks to promote cultural belonging and identity development in their children. In spite of this however, there is, to date, no research study that has sought to apply the notion of social capital to understand transracial adoptive families. With its exploration of how white American adoptive mothers construct social capital in raising their transracially adopted children, this paper seeks to contribute to the literature on social capital and families in general, and social capital and transracial families in particular. By drawing upon a qualitative study involving white adoptive mothers’ discursive practices, and multiplex constructions of intersectionality, the paper seeks to offer rich theoretical and empirical insights into social capital and transracial adoption to contribute to the literature in this area.     

Why zygosity of multiple births is not always obvious: an examination of zygosity testing requests from twins or their parents.

This paper examines why parents of twins or adult twins themselves request zygosity testing. Of 405 multiples including 8 sets of triplets, the majority (93%) were monozygotic. Age of testing ranged from 0 days to 73 years. About 50% of requests came from parents or twins who were curious about, or expressed a need to be certain of, their zygosity. Other reasons included health concerns (current or future), other twins in the family, and misinformation about zygosity, frequently because of the erroneous assumption that all dichorionic twins are dizygotic. Parents of monozygotic twins may expect their twins to be 'identical' and believe their twins to be dizygotic because of minor phenotypic differences between them. Dizygotic twins like other siblings may share a phenotypic resemblance. Health professionals should be aware that zygosity of multiples may not always be obvious to parents and that accurate knowledge of zygosity may be justified.     

Color perception in twins

The classical twin method was used to examine the genotype--phenotype relationship in color vision. Suprathreshold color differences were assessed by 5 pairs of monozygotic (MZ) and 3 pairs of dizygotic (DZ) twins. The control group included 3 unrelated normal trichromats, a non-twin sibling pair, and a previously diagnosed deuteranomal. Concordance rates were calculated by Spearman's correlation coefficients (rs) and Procrustean distances (gl) between the reconstructed color spaces for each related pair of observers. For 4 pairs of the MZ twins, the rs values were comparable to intraindividual variability in the control normal trichromat; they were significantly higher (0.94-0.97) than those for the DZ twins and siblings (0.72-0.82). The gl values for the MZ twins (0.008-0.029) were lower than for the DZ twins (0.073-0.079) and siblings (0.053). The high concordance between each pair of the MZ twins suggests that their shared photopigment genome constrains a contribution of possible individual variations in nongenetic factors to variability of their color spaces. Lower concordance rates in the DZ twins and siblings can be attributed to differences in the inherited arrays of photopigment genes. Contributions to intrapair variation in color spaces of twins from cognitive factors such as perceptual-cognitive color categorization and decision-process variability are discussed.     

Recruitment and attrition in twin register studies of childhood behavior: the example of the Australian Twin ADHD Project.

There are a growing number of large-scale initiatives for twin registers of children. The Australian Twin ADHD Project (ATAP) is used to illustrate two key limitations which may arise with such studies, namely (1) the importance of including or possibly excluding families in which one or both twins have significant developmental disability, and (2) the selective failure to recruit and/or the selective attrition of families in which parents and children share behavioral difficulties. Initially ATAP excluded 1 in 6 of families whose twins were enrolled in the volunteer-based Australian Twin Registry (ATR), and as more children with significant problems were identified, these families were sequentially excluded. With longitudinal data over ten years, two points about retention were identified: the difficulty of retaining the twins in late adolescence, and the loss of the families whose twins had more ADHD symptoms. We discuss strategies for limiting the loss of families and for ensuring comparability of data across registers with similar interests but different methods of recruitment and exclusion.     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809–822, 2001)     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809-822, 2001)     

Comparing blood pressure of twins and their singleton siblings: being a twin does not affect adult blood pressure.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.     

Intelligence and family size: A paradox resolved

Abstract

IQ data was studied for over a thousand families for both parents and offspring, and also for the non‐reproducing siblings of parents. The inclusion of these siblings allowed the authors to resolve the paradox presented by the failure of the general intelligence level to decline in accord with the large negative correlation (‐0.30) between intelligence and number of children in the family. When the non‐reproducing siblings of the parents are included, the negative correlation disappears. The higher reproductive rate of individuals in the lower IQ groups who are parents is offset by the larger proportion of their siblings who never marry or who fail to reproduce when married. Thus, the IQ level of the whole population should remain relatively static from one generation to the next, or at least not drop rapidly.     

Chinese National Twin Registry as a resource for genetic epidemiologic studies of common and complex diseases in China.

Twins, due to their unique genetic and environmental relationships, have provided crucial insight in our understanding of genetic contributions to numerous etiologically complex disorders in developed countries. As the leading cause of death and adult disability, cardio- and cerebrovascular diseases are common in China, followed by cancer. Obesity and psychological disorders are increasing. The overall goal of this program is to develop a resource for genetic epidemiologic studies of these and other common and complex diseases in China. Our initial focus is to delineate the genetic and environmental determinants of vascular diseases in general, coronary artery disease (CAD) and stroke in particular. To date, we have over 4500 twin pairs registered and about 700 twin pairs studied for various metabolic traits (e.g., lipids, glucose, insulin, etc.). The long-term plan of this program is to (1) establish a population-based twin registry from several selected regions in China for future studies of specific common complex diseases; (2) conduct detailed phenotyping for clinical and intermediate traits related to cardiovascular diseases; (3) expand studies of twins to twin families by including their parents, siblings, and offspring for genetic linkage and association studies; and (4) follow up twins in the registry longitudinally. The goals of the program are health education and promotion of healthy behavior, early identification of cases to provide timely medical attention, and the evaluation of long-term effects of identified risk factors. We want to develop collaborations with investigators who have expertise in cancer, psychological disorders, and other disease areas.     

A family study of anthropometric traits in a Punjabi community: I. Introduction and familial correlations

Data on 40 anthropometric measurements from 144 nuclear families in Chandigarh, India, are presented. Most families contain a pair of monozygotic or dizygotic twins, one or more singleton siblings, and their parents. Familial correlations for age-sex standardized, normalized measurements are estimated by maximum likelihood for marital, parent-child, sibling, and twin pairs. Heterogeneity tests for sex-specific subtype correlations male-male, male-female, female-female) indicate that the sex of the relative plays no significant role in the magnitude of the familial correlations except for maternal effects and differences among male and female twin pairs for a few of the variables. Marital correlations are high for body measurements, but not for head or face variables. Twin correlations seem to indicate a higher level of heritability than correlations from other family members.     

Sociodemographics of Pet Ownership among Adolescents in Great Britain: Findings from the HBSC Study in England,Scotland, and Wales

The aim of this study was to assess the prevalence of pet ownership among adolescents in Great Britain and identify any sociodemographic differences between pet owners and non-pet owners. A total of 14,328 11-to 15-year-old adolescents from England, Scotland, and Wales were included in the analysis. Results revealed 15-year-old adolescents were significantly more likely than 11-year-old adolescents to own dogs (OR = 1.146, p < 0.001) but less likely to own fish, reptiles, or amphibians (OR = 0.629, p < 0.001), and small mammals (OR = 0.630, p < 0.001). Thirteen-year-olds were significantly more likely than 11-year-olds to own dogs (OR = 1.240, p = 0.021) and birds (OR = 1.299, p = 0.010), but significantly less likely to own fish, reptiles, or amphibians (OR = 0.795, p < 0.001). No gender differences were found. White adolescents were more likely than non-white adolescents to own all pet types. Those living in single-parent families were significantly more likely than those living with two parents to own dogs (OR = 1.186, p = 0.013) and cats (OR = 1.319, p < 0.001). Furthermore, those who reported living in stepfamilies were also more likely to own cats (OR = 1.428, p < 0.001). Adolescents with siblings were more likely to own cats (OR = 1.391, p = 0.001), fish, reptiles, or amphibians (OR = 1.220, p = 0.037) than adolescents without siblings. Adolescents with employed parents (both or one) were significantly more likely than those with unemployed parents to own dogs (OR = 1.414, p = 0.002) and birds (OR = 1.523, p = 0.018). Adolescents from high-affluence families were less likely than adolescents from low-affluence families to own dogs (OR = 0.888, p = 0.037), small mammals (OR = 0.832, p = 0.005), and birds (OR = 0.801, p = 0.046). Furthermore, family affluence differences were found in different pet types. Differences in all pet types and siblings were also found in a proxy measure of attachment to pets. This study provides evidence that pet ownership is related to several sociodemographic factors. These are relevant to take into account when performing HAI studies on adolescents.