J.H. Stubbe

Netherlands Twin Register: From Twins to Twin Families

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.

Testing causality in the association between regular exercise and symptoms of anxiety and depression.

CONTEXT In the population at large, regular exercise is associated with reduced anxious and depressive symptoms. Results of experimental studies in clinical populations suggest a causal effect of exercise on anxiety and depression, but it is unclear whether such a causal effect also drives the population association. We cannot exclude the major contribution of a third underlying factor influencing exercise behavior and symptoms of anxiety and depression. OBJECTIVE To test causal effects of exercise on anxious and depressive symptoms in a population-based sample. DESIGN Population-based longitudinal study (1991-2002) in a genetically informative sample of twin families. SETTING Causal effects of exercise were tested by bivariate genetic modeling of the association between exercise and symptoms of anxiety and depression, correlation of intrapair differences in these traits among genetically identical twins, and longitudinal modeling of changes in exercise behavior and anxious and depressive symptoms. PARTICIPANTS A total of 5952 twins from the Netherlands Twin Register, 1357 additional siblings, and 1249 parents. All participants were aged 18 to 50 years. MAIN OUTCOME MEASUREMENTS Survey data about leisure-time exercise (metabolic equivalent task hours per week based on type, frequency, and duration of exercise) and 4 scales of anxious and depressive symptoms (depression, anxiety, somatic anxiety, and neuroticism, plus a composite score). RESULTS Cross-sectional and longitudinal associations were small and were best explained by common genetic factors with opposite effects on exercise behavior and symptoms of anxiety and depression. In genetically identical twin pairs, the twin who exercised more did not display fewer anxious and depressive symptoms than the co-twin who exercised less. Longitudinal analyses showed that increases in exercise participation did not predict decreases in anxious and depressive symptoms. CONCLUSION Regular exercise is associated with reduced anxious and depressive symptoms in the population at large, but the association is not because of causal effects of exercise.

Physical Activity and Cognitive Function in a Cross-Section of Younger and Older Community-Dwelling Individuals

Previous reports have indicated a small, positive relationship between physical activity and cognition. However, the majority of research has focused on older adults, with few studies examining this relationship during earlier periods of the life span. This study examined the relationship of physical activity to cognition in a cross-section of 241 community-dwelling individuals 15-71 years of age with a task requiring variable amounts of executive control. Data were analyzed with multiple regression, which controlled for age, sex, and IQ. Participants reported their physical activity behavior and were tested for reaction time (RT) and response accuracy on congruent and incongruent conditions of a flanker task, which manipulates interference control. After controlling for confounding variables, an age-related slowing of RT was observed during both congruent and incongruent flanker conditions. However, physical activity was associated with faster RT during these conditions, regardless of age. Response accuracy findings indicated that increased physical activity was associated with better performance only during the incongruent condition for the older cohort. Findings suggest that physical activity may be beneficial to both general and selective aspects of cognition, particularly among older adults.

Sports participation during adolescence: a shift from environmental to genetic factors

PURPOSE A twin design was used to assess the relative contribution of genetic and environmental influences on the variation in sports participation of Dutch male and female twins between the ages of 13 and 20 yr. METHODS Survey data from 2628 complete twin pairs were available (443 male and 652 female monozygotic twin pairs, 377 male and 434 female dizygotic twin pairs, and 722 opposite-sex twin pairs). Subjects were classified as participating in sports if they engaged in competitive or noncompetitive leisure-time sports activities with a minimal intensity of 4 METs for at least 60 min.wk. RESULTS An overall main effect of age and sex was found on the sports participation dichotomy. Younger twins participated more in sports than older twins, and for each age group males participated more often than females. Genetic analyses of twin resemblance showed a shift in the factors contributing to sports participation from adolescence to adulthood. Between the ages of 13 and 16 yr, environmental factors shared by children from the same family largely account for individual differences in sports participation (78-84%), whereas genes are of no importance. At the age of 17-18 yr, genetic influences start to appear (36%), and the role of common environment decreases (47%). After the age of 18 yr, genes largely explain individual differences in sports participation (85%), and common environmental factors no longer contribute. CONCLUSIONS Environmental factors shared by family members determine sports participation in young adolescence but cease to be of importance in adulthood when individual differences in sports participation are largely due to genetic variation.

Heritability of life satisfaction in adults: a twin-family study

BACKGROUND Subjective well-being (SWB) can be partitioned into the components life satisfaction and affect. Research on factors influencing these components of well-being has mainly focused on environmental characteristics. The aim of this study was to investigate the relative contribution of genes and environment to individual differences in life satisfaction in a large sample of Dutch twins and their singleton siblings. METHOD Life satisfaction of 5668 subjects registered with The Netherlands Twin Registry (NTR) was measured with a Dutch version of the self-reported Satisfaction with Life Scale. An extended twin design was used to obtain correlations in life satisfaction scores for monozygotic twins, dizygotic twins and sibling pairs and to estimate the contribution of genes and environment to the variation in life satisfaction. RESULTS No differences between males and females were found in the mean level of life satisfaction. Broad-sense heritability was 38%. Non-additive genetic factors explained all or most of the genetic influences. The remaining 62% of the variance in life satisfaction could be attributed to unique environmental factors, both persistent and transitory, plus measurement error. CONCLUSIONS Individual differences in life satisfaction are determined in part by genetic factors that are largely or entirely non-additive in nature.

Effectiveness of an injury prevention programme for adult male amateur soccer players: a cluster-randomised controlled trial

Background The incidence rate of soccer injuries is among the highest in sports, particularly for adult male soccer players. Purpose To investigate the effect of the ‘The11’ injury prevention programme on injury incidence and injury severity in adult male amateur soccer players. Study design Cluster-randomised controlled trial. Methods Teams from two high-level amateur soccer competitions were randomly assigned to an intervention (n=11 teams, 223 players) or control group (n=12 teams, 233 players). The intervention group was instructed to perform The11 in each practice session during one soccer season. The11 focuses on core stability, eccentric training of thigh muscles, proprioceptive training, dynamic stabilisation and plyometrics with straight leg alignment. All participants of the control group continued their practice sessions as usual. Results In total, 427 injuries were recorded, affecting 274 of 456 players (60.1%). Compliance with the intervention programme was good (team compliance=73%, player compliance=71%). Contrary to the hypothesis, injury incidences were almost equal between the two study groups: 9.6 per 1000 sports hours (8.4–11.0) for the intervention group and 9.7 (8.5–11.1) for the control group. No significant differences were found in injury severity, but a significant difference was observed in the location of the injuries: players in the intervention group sustained significantly less knee injuries. Conclusions This study did not find significant differences in the overall injury incidence or injury severity between the intervention and control group of adult male soccer players. More research is recommended, focusing on injury aetiology and risk factors in adult male amateur soccer players.

Estimating non-response bias in family studies: application to mental health and lifestyle.

Non-response to mailed surveys reduces the effective sample size and may introduce bias. Non-response has been studied by (1) comparison to available data in population based registers, (2) directly contacting non-respondents by telephone or single-item reply cards, and (3) longitudinal repetition of the survey. The goal of this paper was to propose an additional method to study non-response bias: when the variable of interest has a familial component, data from respondents can be used as proxy for the data from their non-responding family members. This approach was used with data on smoking, alcohol consumption, physical activity, coffee- and tea-use, education, body mass index, religion, burnout, life events, personality and mental health in large number of siblings and DZ twins registered with the Netherlands Twin Register. In addition, for smoking behavior, we also used the second strategy by sending a reply card. Results show that scores of members from less cooperative families or incomplete twin pairs tended to be more unfavorable than the scores from highly cooperative families or complete twin pairs. For example, family members from less cooperative families cycled less often and scored higher on anxious depression and neuroticism. For smoking, both the results of the reply card and the results of the additional method suggested a higher percentage smokers among the non-respondents but this was only significant with reply card method. In general, differences between highly/less cooperative families and complete/incomplete DZ twins were small. Results suggest that, even for studies with moderate response rates, data collected on health, personality and lifestyle are relatively unbiased.

Migraine with Aura and Migraine without Aura are not Distinct Entities: Further Evidence from a Large Dutch Population Study

It is often debated whether migraine with aura (MA) and migraine without aura (MO) are etiologically distinct disorders. A previous study using latent class analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO and MA. The aim of the present study was to replicate these results in a population of Dutch twins and their parents, siblings and partners (N = 10,144). Latent class analysis of International Headache Society (IHS)-based migraine symptoms resulted in the identification of 4 classes: a class of unaffected subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately severe type of migraine (class 2), typically without neurological symptoms or aura (8% reporting aura symptoms), and a severe type of migraine (class 3), typically with neurological symptoms, and aura symptoms in approximately half of the cases. Given the overlap of neurological symptoms and nonmutual exclusivity of aura symptoms, these results do not support the MO and MA subtypes as being etiologically distinct. The heritability in female twins of migraine based on LCA classification was estimated at .50 (95% confidence intervals [CI] .27 - .59), similar to IHS-based migraine diagnosis (h2 = .49, 95% CI .19-.57). However, using a dichotomous classification (affected-unaffected) decreased heritability for the IHS-based classification (h2 = .33, 95% CI .00-.60), but not the LCA-based classification (h2 = .51, 95% CI .23-.61). Importantly, use of the LCA-based classification increased the number of subjects classified as affected. The heritability of the screening question was similar to more detailed LCA and IHS classifications, suggesting that the screening procedure is an important determining factor in genetic studies of migraine.

The relationship between the frequency of football practice during skeletal growth and the presence of a cam deformity in adult elite football players

Background/aim Cam deformity (CD) is likely a bony adaptation in response to high-impact sports practice during skeletal growth. We ascertained whether a dose–response relationship exists between the frequency of football practice during skeletal growth and the presence of a CD in adulthood, and if the age at which a football player starts playing football is associated with the presence of a CD in adulthood. Methods Prevalence of a CD (α angle>60°) and a pathological CD (α angle>78°) was studied using standardised anteroposterior (AP) and frog-leg lateral (FLL) radiographs that were obtained during seasonal screening. The age of starting to play football with a low frequency (LF; ≤3 times/week) and high frequency (HF; ≥4 times/week) was retrospectively assessed. The differences in prevalence of a CD per hip, in either view, between groups were calculated by logistic regression with generalised estimating equations. Results 63 players (mean(±SD) age 23.1(±4.2) years) participated, yielding 126 hips for analysis. The prevalence of a CD in the FLL was 40% (n=82) in players who started playing HF football from the age of 12 years or above, and 64% (n=44) in those playing HF football before the age of 12 years (p=0.042). This was also true for a pathological CD (12% vs 30%, p=0.038). The AP views revealed no difference. Conclusions Our results indicate a probable dose–response relationship between the frequency of football practice during skeletal growth and the development of a CD, which should be confirmed in future prospective studies.

Differences in injury risk and characteristics between Dutch amateur and professional soccer players

OBJECTIVES To compare the incidence and characteristics of injuries between Dutch amateur and professional male soccer players during one entire competition season. DESIGN A prospective two-cohort design. METHODS During the 2009-2010 season, 456 Dutch male amateur soccer players and 217 professional players were prospectively followed. Information on injuries and individual exposure to all soccer activities were recorded in both cohorts. Injuries were recorded using the time-loss definition. RESULTS In total, 424 injuries were recorded among 274 of the amateur players (60.1% injured players) and 286 injuries were sustained by 136 (62.7% injured players) of the professional players (p=0.52). Compared to the professionals, the injury incidence during training sessions was higher among amateurs (p=0.01), but the injury incidence among professionals was higher during matches (p<0.001). Professional players also had a higher incidence of minimal injuries (p<0.001), whereas the incidence of moderate and severe injuries was higher for amateurs (all p<0.001). Lastly, professional players sustained more overuse injuries (p=0.02), whereas amateurs reported more recurrent injuries (p<0.001). CONCLUSIONS The above-mentioned differences in injury rates between amateur and professional players in the Netherlands might be explained by the difference in the level at which they play, since factors like the availability of medical support and/or the team size may influence the injury risk and characteristics.