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Item does not contain fulltext, The aim of this study is to examine an extended model of the Theory of Planned Behavior (TPB) and increase insight into the intentions to consume energy-dense food among adolescents in Indonesia. This study included 411 adolescents from private schools who reported their intentions to consume energy-dense food the next day and the next week, as well as attitudes, subjective norms, descriptive norms, and perceived behavioral control regarding energy-dense food consumption. Linear regression analyses (in R) were conducted to examine associations of TPB determinants (model 1), TPB determinants plus descriptive norms (model 2), and interactions between determinants (model 3) with the intention to consume energy-dense food the (1) next day or (2) next week. Attitudes and subjective norms were positively associated with both the 'next day' and 'next week' energy-dense food intentions (model 1), although associations for the 'next day model' appeared to be stronger. Descriptive norms, compared to subjective norms, were more strongly associated with 'next week intentions', whereas both norms (descriptive and subjective) did not differ in how strongly they were associated with 'next day' intentions (model 2). Significant interactions between TPB constructs were found for the model predicting ‘next day’ intentions (i.e. subjective norms × attitude and attitude × PBC) (model 3). Our study provides important information about proximal food intentions among collectivistic cultures specifically, which may have crucial implications for future preventive interventions.

Radboud University, 19 januari 2023, Promotor : Vink, J.M. Co-promotores : Larsen, J.K., Verhagen, M., Burk, W.J., Contains fulltext : 286141.pdf (Publisher’s version ) (Open Access), Many adolescents opt for a slice of pizza instead of an apple. Why? This dissertation offers unique insights into this question by following adolescents themselves, their mothers, and their best friends over the first years of high school. It was revealed that the food intake of mothers, and less that of best friends, was associated with the development of adolescents’ (un)healthy food intake. For example, the results showed that when mothers snacked more unhealthily, adolescents themselves snacked more later on. The importance of mothers was also demonstrated during the coronacrisis. For instance, it was found that while, on average, adolescents' fruit and vegetable intake had permanently decreased after the first corona-lockdown, this decrease was not permanent for adolescents whose mothers consumed more fruits and vegetables. Their fruit and vegetable intake returned to pre-pandemic levels. In summary, the apple does not seem to fall that far from the tree.

Contains fulltext : 282337.pdf (Publisher’s version ) (Open Access), Genetic factors have a substantial influence on individuals' food preferences, but less is known about their influence on abstinence from eating meat and fish. Here we looked at the influence genetics may have on pescetarianism (not eating meat but eating fish) and vegetarianism (not eating meat and fish) in a Dutch twin sample (N = 8196). We also examined genetic and environmental influences on abstinence from eating beef, pork, poultry, fish or shellfish separately and explored the reasons individuals gave for not eating these types of meat and fish (e.g., disliking, health concerns or beliefs). Abstinence from eating various meats or (shell)fish varied from 5.3% for beef to 46% for shellfish, and 3.7% did not eat meat (1.9% was pescatarian and 1.8% vegetarian). The prevalence of all abstinences was higher in women than men. Genetic factors accounted for 74% and 77% of variation in pescetarianism and vegetarianism, respectively, with the remaining variance accounted for by non-shared environmental influences. Heritability for abstinence from eating beef, pork, poultry, fish or shellfish ranged from 70 to 80%. Abstention from pork was mostly due to health concerns, abstention from poultry, fish and shellfish because of dislike, and abstention from beef because of beliefs (i.e., religion or convictions). Most pescatarians and vegetarians reported beliefs as one of their reason for abstinence (∼75%). Overall, regardless of the fact that different reasons seem to play a role in pescetarianism, vegetarianism and abstinence from eating different meats and fish, genetic factors undergirded all with a similar large magnitude.

Item does not contain fulltext, The COVID-19 pandemic may negatively influence food parenting practices, also among parents of adolescents. Parental well-being (stress and depressive symptoms) may explain these COVID-19 related changes in food parenting practices (snack structure, healthy structure, modeling, autonomy support, and coercive control). However, most previous studies performed before or during the COVID-19 pandemic have been limited by cross-sectional designs. The aim of the current study among parents of adolescent children was twofold. First, we aimed to examine prospective differences in food parenting practices comparing the situation before and during COVID-19. Second, we aimed to examine both cross-sectional and longitudinal associations between parental well-being and the dimensions of food parenting, while additionally examining whether these prospective associations were more pronounced in parents who had experienced more COVID-19 stressful life events. Parents (N = 290; 74.9% female; at baseline: Mage = 46.9; SDage = 4.3) of adolescent children (at baseline: Mage = 14.3; SDage = 0.6) completed online surveys about parental well-being and food parenting twice: One year before the COVID-19 pandemic (spring 2019) and during the COVID-19 pandemic, 1.5 years after the first measurement (autumn 2020). In general, we found consistent evidence for an average decrease in food autonomy support and an increase in coercive control during COVID-19. However, parental well-being did not seem to explain (changes in) food parenting practices during COVID-19, also not in combination with stressful life events. Our findings suggest that, regardless of parental well-being, the general COVID-19 situation had some small negative influences on autonomy support and coercive control among parents of adolescents. These findings might be explained by parents being more often confronted with unhealthy eating occasions in the COVID-19 home context, triggering these negative parental responses.

19 februari 2023, Item does not contain fulltext, Objective: Schools are considered an important setting for stimulating healthy weight. The current study is unique in examining effects of a multi-component school-based social network intervention on children’s body mass index z-scores (zBMI). Methods: Four schools were randomly allocated to one of four conditions: a social network intervention using influence agents focusing on water consumption, physical activity, a combination of the two, or a passive control condition. Participants included a total of 201 6- to-11-year-old children (53.7% girls; Mage = 8.51, SDage = 0.93). At baseline, 149 (76.0%) participants had a healthy weight, 29 (14.8%) had overweight and 18 (9.2%) had obesity. Results: Linear mixed effect models indicated that a multi-component school-based social network intervention targeting both water consumption and physical activity was most effective in decreasing children’s zBMI. Conclusion: This study suggests that schools can contribute to the intervention of childhood obesity - even without involving the parents - by targeting both children’s water consumption and physical activity through influential peers, but more research is needed to identify mechanisms of change.

Item does not contain fulltext, Rationale: The first COVID-19 lockdown impacted the social life and behaviors of university students, such as alcohol use. While previous studies have reported changes in students' alcohol use during the lockdown, knowledge of risk groups like binge drinkers is limited. Objective: The purpose of this study is to investigate how the first lockdown impacted the alcohol use of university students who were regular binge drinkers before the lockdown. Methods; Cross-sectional data were used to explore self-reported changes in alcohol use and associated psychosocial effects in regular binge drinking versus regular drinking university students (N = 7355) during the first COVID-19 lockdown (Spring 2020) in the Netherlands. Results: University students generally drank less alcohol and reduced binge drinking behaviors during the lockdown. Being a binge drinker who increased/maintained alcohol use, or a regular drinker who increased, was associated with older age, fewer servings of alcohol per week before COVID-19, higher contact with friends, and not living with parents. Among regular binge drinkers, men increased their alcohol use during the lockdown significantly more than women. Among regular drinkers, those with high depressive symptoms and low resilience had increased alcohol use. Conclusions: These findings give insight into significant changes in drinking behaviors among university students during the first COVID-19 lockdown. More importantly, it underscores the need to reckon vulnerable students considering drinking type and associated psychosocial variables for increasing or maintaining higher alcohol use during societal stress periods. In the present study, an unexpected at-risk group emerged among regular drinkers who increased alcohol use during the lockdown in association with their mental state (i.e., depression and resilience). As the COVID-19 pandemic, and the possibility of similar scenarios in the future, is still present in the current student life, specific

Contains fulltext : 295460.pdf (Publisher’s version ) (Open Access), The college years represent a vulnerable period for developing health-risk behaviours (e.g., physical inactivity/unhealthy eating habits/substance use/problematic internet use/insufficient sleep). This study examined current health behaviour levels (RQ1), health behaviour classes (RQ2) and between-class differences in socio-demographics (RQ3) and mental well-being (RQ4) among Dutch university students (n = 3771). Participants (Mage = 22.7 (SD = 4.3); 71.2% female/27.3% male/1.5% other) completed an online survey (Oct-Nov 2021). Descriptive statistics (RQ1), Latent Class Analysis (RQ2), and Kruskal-Wallis/Chi-square tests (RQ3-4) were used. RQ1: Prevalence rates suggest that a subsequent proportion of the student sample engages in health-risk behaviours. RQ2: Four classes were identified: class 1 (n = 862) "Licit substance use health-risk group", class 2 (n = 435) "Illicit and licit substance use health-risk group", class 3 (n = 1876) "Health-protective group" and class 4 (n = 598) "Non-substance use health-risk group". RQ3: Class 1 represents relatively more international students and students in a steady relationship. Class 2 represents relatively more older/male/(pre-)master students and students living with roommates/in a steady relationship/with more financial difficulty. Class 3 represents relatively more younger/female students and students living with family/with lower Body Mass Index (BMI)/less financial difficulty. Class 4 represents relatively more younger/non-Western/international/bachelor students and students living with children/single/part of LGBTIQ+ community/with higher BMI. RQ4: Class 3 has significantly higher mental well-being while class 4 has significantly lower mental well-being, relative to the other classes. Above findings provide new insights which can help educational institutes and governments better understand the clustering of students' health behaviours and between-class differences in socio-demographics and mental well-being.

20 juni 2023, Item does not contain fulltext, Sleep has a profound effect on our mood, but insight in the mechanisms underlying this association is still lacking. We tested whether emotion regulation is a mediator in the relationship between fragmented sleep and mood disturbance. The effect of fragmented sleep on the emotion regulation strategies, including cognitive reappraisal, distraction, acceptance and suppression ability, was assessed. We further tested whether the use of these strategies, as well as rumination and self-criticism, mediated the association between fragmented sleep and negative and positive affect. Participants (N = 69) wore an actiwatch and filled in a sleep diary for 12 consecutive nights. They had one control night and one sleep fragmentation night. Emotion regulation ability was assessed with an experimental task. Usage of emotion regulation strategies and negative and positive affect were assessed four times during the day with a survey after the control and sleep fragmentation night. Cognitive reappraisal, distraction, acceptance and suppression ability did not differ between the sleep fragmentation and control condition. However, participants reported higher usage of rumination and distraction after the sleep fragmentation night and rumination significantly mediated the negative association between fragmented sleep and negative affect.

Contains fulltext : 298877.pdf (Publisher’s version ) (Open Access), Cannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9436 participants (7795 European and 1641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05 $$(p < 5.85\times {10}^{-7})$$: cg22572071 near gene ADGRF1, cg15280358 in ADAM12, cg00813162 in ACTN1, and cg01101459 near LINC01132. Additionally, our EWAS analysis in participants who never smoked cigarettes identified another epigenome-wide significant CpG site, cg14237301 annotated to APOBR. We used a leave-one-out approach to evaluate methylation scores constructed as a weighted sum of the significant CpGs. The best model can explain 3.79% of the variance in lifetime cannabis use. These findings unravel the DNA methylation changes associated with lifetime cannabis use that are independent of cigarette smoking and may serve as a starting point for further research on the mechanisms through which cannabis exposure impacts health outcomes., 07 november 2023, 10 p.

Item does not contain fulltext, This study aims to disentangle the contribution of genetic liability, educational attainment (EA), and their overlap and interaction in lifetime smoking. We conducted genome-wide association studies (GWASs) in UK Biobank (N = 394,718) to (i) capture variants for lifetime smoking, (ii) variants for EA, and (iii) variants that contribute to lifetime smoking independently from EA ('smoking-without-EA'). Based on the GWASs, three polygenic scores (PGSs) were created for individuals from the Netherlands Twin Register (NTR, N = 17,805) and the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2, N = 3090). We tested gene–environment (G x E) interactions between each PGS, neighborhood socioeconomic status (SES) and EA on lifetime smoking. To assess if the PGS effects were specific to smoking or had broader implications, we repeated the analyses with measures of mental health. After subtracting EA effects from the smoking GWAS, the SNP-based heritability decreased from 9.2 to 7.2%. The genetic correlation between smoking and SES characteristics was reduced, whereas overlap with smoking traits was less affected by subtracting EA. The PGSs for smoking, EA, and smoking-without-EA all predicted smoking. For mental health, only the PGS for EA was a reliable predictor. There were suggestions for G × E for some relationships, but there were no clear patterns per PGS type. This study showed that the genetic architecture of smoking has an EA component in addition to other, possibly more direct components. PGSs based on EA and smoking-without-EA had distinct predictive profiles. This study shows how disentangling different models of genetic liability and interplay can contribute to our understanding of the etiology of smoking.

Contains fulltext : 247361.pdf (Publisher’s version ) (Open Access), (1) Background: Few studies have investigated (demographic) correlates of (prevalent) overweight rates among early adolescents, especially from higher socioeconomic positions (SEP) in developing countries, such as Indonesia. The current study aims to fill this gap. (2) Methods: Participants included 411 adolescents from five private schools in Indonesia. Adolescents' weight and height were measured, and adolescents completed questionnaires on demographic factors (i.e., sex, school area, ethnicity, pocket money) and previous year dieting. (3) Results: Results showed that more than one-third of the sample was overweight, with higher rates among adolescent males (47%) than females (24%). Moreover, adolescents attending schools in urban areas (compared with suburban areas), and those reporting past dieting (compared with those reporting no dieting) had higher overweight rates. Ethnicity and the amount of pocket money were not related to overweight status. Finally, a clear sex-specific interaction was found involving school area, showing that males in urban areas had a significantly higher risk to be overweight, whereas this did not apply to females. (4) Conclusions: males from urban area private schools in Indonesia may be an important target group for future preventive overweight interventions.

Radboud University, 27 juni 2022, Promotor : Vink, J.M. Co-promotor : Larsen, J.K., Contains fulltext : 250924.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext, Little is known about how adolescent best friends may affect each other's food intake. This study explored whether friendship selection and socialization mechanisms explained potential food intake similarities in adolescent reciprocated best friend dyads. We also tested whether socialization processes were moderated by dyad member's relative zBMI. Members of 145 same-gender best friendship dyads (56% female; Mage = 12.79; SDage = 0.61) reported on their intake of food obtained from home and from outside the home at the beginning and the end of the school year through food frequency questionnaires. Longitudinal Actor-Partner Interdependence Models results showed no indication of selection or socialization, and very limited evidence for the moderation of socialization processes by relative zBMI. These findings indicate that focusing on adolescent reciprocated best friends in dietary interventions may not be valuable.

Item does not contain fulltext, Background: The freezing response is a universal response to threat, linked to attentive immobility and action preparation. It is relevant for acute stress coping in animals and humans, and subtle deviations in toddler freezing duration (absence of, or excessively long reactions) have been linked to higher risk for internalizing symptoms in adolescence. Yet, while individual freezing tendencies are relatively stable throughout life, little is known about their gene-environment aetiology. Methods: We investigated the heritability of toddler freezing in the Quebec Newborn Twin Study (QNTS; n=508 twins) by fitting behavioural genetic models to video-coded freezing responses during a robot confrontation. Furthermore, we examined the predictive associations between toddler freezing and internalizing symptoms (anxiety and depressive symptoms), as they unfold during adolescence (ages 12–19 years) using linear mixed-effects models. Findings: Freezing was found to be moderately heritable (45% of the variance accounted for by genetic factors). The remaining variance was explained by unique environmental factors, including measurement error. No significant contribution of shared environmental factors was noted. Additionally, shorter freezing was associated with more internalizing symptoms in adolescence at trend level, a pattern that was significant for depressive but not anxiety symptoms. Interpretation: Freezing is an adaptive coping mechanism in early childhood, which is partly driven by genetic factors. Crucially, the absence or shorter duration of these behaviours may signal vulnerability to depressive problems later in life. Funding: Canadian Institutes of Health Research and Research Fund of Quebec–Health and Society and Culture. Consolidator grant from the European Research Council (ERC_CoG-2017_772337).

Contains fulltext : 244352.pdf (Publisher’s version ) (Open Access), Tobacco, alcohol and cannabis are commonly used among university students. However, student lives and their substance use have changed dramatically since the start of the COVID-19 pandemic. This study investigated the impact of COVID-19 on (trends in) weekly smoking, weekly binge drinking and weekly cannabis use in Dutch university students and investigated associated student-, study- and COVID-19-related characteristics. Between April and June 2020, several Dutch higher educational institutes invited their students to participate in an online survey. Data of 9967 students (Mage = 22.0 (SD = 2.6); Nfemale = 7008 (70.3%)) were available for analyses. Overall, weekly smoking remained stable (±11.5%), weekly binge drinking decreased (from 27.8% to 13.9%) and weekly cannabis use increased (from 6.7% to 8.6%). Male gender, not living with parents, being a bachelor student, having less financial resources and less adherence to the COVID-19 measures were found to increase the risk of substance use (before/during the first COVID-19 lockdown). Additionally, male gender, not living with parents, being a bachelor student, not being born in the Netherlands and having a student loan contributed to the likelihood of increased substance use during COVID-19. Patterns of characteristics contributing to the likelihood of decreased weekly substance use during COVID-19 were less clear. The risk factors male gender, not living with parents and being a bachelor student do not only contribute to the likelihood of using substances but also contribute to the likelihood of increased use during a lockdown. Prevention and intervention programs should especially target these risk groups.

Item does not contain fulltext, The cell adhesion molecule 2 (CADM2) gene has appeared among the top associations in a wide range of genome-wide association studies (GWASs). This study aims to: (1) examine how widespread the role of CADM2 is in behavioural traits, and (2) investigate trait-specific effects on CADM2 expression levels across tissues. We conducted a phenome-wide association study in UK Biobank (N = 12,211–453,349) on 242 psycho-behavioral traits, both at the SNP and the gene-level. For comparison, we repeated the analyses for other large (and high LD) genes. We found significant associations between CADM2 and 50 traits (including cognitive, risk taking, and dietary traits), many more than for the comparison genes. We show that many trait associations are reduced when taking geographical stratification into account. S-Predixcan revealed that CADM2 expression in brain tissues was significantly associated with many traits; highly significant effects were also observed for lung, mammary, and adipose tissues. In conclusion, this study shows that the role of CADM2 extends to a wide range of psycho-behavioral traits, suggesting these traits may share a common biological denominator.

15 september 2022, Contains fulltext : 253757.pdf (Publisher’s version ) (Open Access), Although insight in how adolescents' food intake is affected by the COVID-19 pandemic is critical, knowledge is limited. Hence, this longitudinal study (N = 691, Mage = 14.30, SDage = 0.62; 52.5% female) investigated changes in adolescents' unhealthy (sugar-sweetened beverages, sweet snacks, savoury snacks) and healthy (fruit and vegetables) food intake (in total, obtained from home, and from outside the home) from pre-pandemic (Spring 2019) to the first lockdown (Spring 2020) and to six months later (Fall 2020). Moreover, several moderating factors were assessed. Results showed that the intake of unhealthy and healthy food in total and obtained from outside the home decreased during the lockdown. Six months later, unhealthy food intake returned to pre-pandemic levels, while healthy food intake remained lower. COVID-19 stressful life events and maternal food intake further qualified these longer-term changes in intake of sugar-sweetened beverages and fruit and vegetables, respectively. Future work is warranted to elucidate longer-term COVID-19 effects on adolescents' food intake.

Contains fulltext : 285187.pdf (Publisher’s version ) (Open Access), Cannabis is among the most widely consumed psychoactive substances worldwide. Individual differences in cannabis use phenotypes can partly be explained by genetic differences. Technical and methodological advances have increased our understanding of the genetic aetiology of cannabis use. This narrative review discusses the genetic literature on cannabis use, covering twin, linkage, and candidate-gene studies, and the more recent genome-wide association studies (GWASs), as well as the interplay between genetic and environmental factors. Not only do we focus on the insights that these methods have provided on the genetic aetiology of cannabis use, but also on how they have helped to clarify the relationship between cannabis use and co-occurring traits, such as the use of other substances and mental health disorders. Twin studies have shown that cannabis use is moderately heritable, with higher heritability estimates for more severe phases of use. Linkage and candidate-gene studies have been largely unsuccessful, while GWASs so far only explain a small portion of the heritability. Dozens of genetic variants predictive of cannabis use have been identified, located in genes such as CADM2, FOXP2, and CHRNA2. Studies that applied multivariate methods (twin models, genetic correlation analysis, polygenic score analysis, genomic structural equation modelling, Mendelian randomisation) indicate that there is considerable genetic overlap between cannabis use and other traits (especially other substances and externalising disorders) and some evidence for causal relationships (most convincingly for schizophrenia). We end our review by discussing implications of these findings and suggestions for future work.

Contains fulltext : 234454.pdf (Publisher’s version ) (Open Access), Background: Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. Aims We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. Method: Mendelian randomisation uses genetic variants predictive of a certain 'exposure' as instrumental variables to test causal effects on an 'outcome'. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results: There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

Item does not contain fulltext, Suitable instruments for measuring Food Parenting Practices (FPP) among adolescents and their parents that also measure the perception of adolescents about their parent's FPP are rare. The current study describes the development and preliminary testing of a short 16-item Adolescent Food Parenting Questionnaire (AFPQ) for parents (AFPQ-p) and adolescents (AFPQ-a) that may enable future large-scale research on potentially eminent parent-child FPP discrepancy. Participants included 381 parents (73.8 % mothers; Mage 45.9, 26.2% fathers; Mage 49.1) and their adolescent children (aged 12-16) who participated in the Dutch "G(F)OOD together" study. Most parents finished higher professional education (mothers: 44.3 %; fathers: 34.4 %) and performed a paid job of 32 h per week or more (mothers: 22.1 %; fathers: 60.0 %). The theoretical framework of Vaughn (2016) was leading in the development of the AFPQ. Exploratory factor analysis (EFA) was performed on a random split sample of parent-adolescent dyads and confirmatory factor analysis (CFA) was performed on the other half. The EFA in both parent and adolescent samples resulted in a clear 5 factor solution explaining 61.6 % (AFPQ-p) and 64.2 % (AFPQ-a) of the variance respectively, representing the factors Autonomy Support (α = 0.79/.82), Coercive Control (α = 0.85/.83), Snack Structure (α = 0.79/75), Healthy Structure (α = 0.78/74) and Modelling (α = 0.69/85). CFA confirmed good model fit for the AFPQ-p and the AFPQ-a. Associations with adolescent self-reported food intake were in the expected direction, confirming the preliminary convergent validity of the instrument among a moderate to highly educated group of parent-adolescent dyads. Although the AFPQ provides a promising short instrument, future research in more diverse samples is needed to build evidence on the instrument's psychometric characteristics in other groups.

Contains fulltext : 232259.pdf (Publisher’s version ) (Open Access), Background: Growing evidence suggests that maternal mental health issues are associated with (young) children's weight outcomes. However, most studies have been limited by cross-sectional designs and have been aimed at (younger) children. The current prospective study focuses on the link between maternal mental health (i.e., psychological stress and depressive symptoms) and adolescents' zBMI development. Methods: The participants in the present study were part of wave 1 and 2 of a longitudinal study on Dutch adolescents' and their parents' health behavior. Adolescents (aged 10-14) and their parents were recruited through six secondary schools in the South and the East of the Netherlands. For this study, we only included biological mothers and their adolescent children who participated in both waves, with data on the main measures in both waves, leaving a final sample of 336 biological mother-child dyads. Adolescents height and weight were measured, and both parents and adolescents filled in validated questionnaires on perceived stress and depressive symptoms and answered additional questions concerning domain-specific stress. Regression analyses were performed in R to examine longitudinal links between maternal stress and depressive symptoms at baseline (T1) and adolescents' BMI standard deviation scores (zBMI) 6 months later (T2), corrected for baseline zBMI and covariates. Results: Maternal general perceived stress (ß = .20, p = .002) at T1 preceded higher adolescents’ zBMI at T2, after controlling for baseline zBMI and other covariates, whereas maternal depressive symptoms at T1 (ß = -.05, p = .44) and other domain-specific stress did not (maternal financial stress, maternal stress at work, maternal stress at home). Additionally, lower educational level among adolescents (β = .16, p = .001) and adolescent depressive symptoms (ß = .16, p = .001) was associated with a higher zBMI at T2. Conclusions: Results suggest that maternal general stress, but not depressive s

28 september 2021, Item does not contain fulltext, Many adolescents start using tobacco, alcohol, and cannabis. Genetic vulnerability, parent characteristics in young adolescence, and interaction (GxE) and correlation (rGE) between these factors could contribute to the development of substance use. Using prospective data from the TRacking Adolescent Individuals' Lives Survey (TRAILS; N = 1,645), we model latent parent characteristics in young adolescence to predict young adult substance use. Polygenic scores (PGS) are created based on genome-wide association studies (GWAS) for smoking, alcohol use, and cannabis use. Using structural equation modeling we model the direct, GxE, and rGE effects of parent factors and PGS on young adult smoking, alcohol use, and cannabis initiation. The PGS, parental involvement, parental substance use, and parent-child relationship quality predicted smoking. There was GxE such that the PGS amplified the effect of parental substance use on smoking. There was rGE between all parent factors and the smoking PGS. Alcohol use was not predicted by genetic or parent factors, nor by interplay. Cannabis initiation was predicted by the PGS and parental substance use, but there was no GxE or rGE. Genetic risk and parent factors are important predictors of substance use and show GxE and rGE in smoking. These findings can act as a starting point for identifying people at risk.

Item does not contain fulltext, Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 x 10(-8)) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r(G) = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders. A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.

24 juni 2021, Item does not contain fulltext, Background: Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. Aims We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. Method: Mendelian randomisation uses genetic variants predictive of a certain 'exposure' as instrumental variables to test causal effects on an 'outcome'. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results: There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

Contains fulltext : 221920.pdf (Publisher’s version ) (Open Access), People with attention-deficit/hyperactivity disorder (ADHD) or other psychiatric disorders show high rates of nicotine dependence (ND). This comorbidity might be (partly) explained by shared genetic factors. Genetic correlations between ND and ADHD (or other psychiatric disorders) have not yet been estimated. A significant genetic correlation might indicate genetic overlap, but could also reflect a causal relationship. In the present study we investigated the genetic correlation (with LD score regression analyses) between ND and ADHD, as well as between ND and other major psychiatric conditions (major depressive disorder, schizophrenia, anxiety, bipolar disorder, autism spectrum, anorexia nervosa, and antisocial behavior) based on the summary statistics of large Genome Wide Association studies. We explored the causal nature of the relationship between ND and ADHD using two-sample Mendelian randomization. We found a high genetic correlation between ND and ADHD (rg = .53, p = 1.85 × 10-13), and to a lesser extent also between ND-major depressive disorder (rg = .42, p = 3.6 × 10-11) and ND-schizophrenia (rg = .18, p = 1.1 × 10-3). We did not find evidence for a causal relationship from liability for ADHD to ND (which could be due to a lack of power). The strong genetic correlations might reflect different phenotypic manifestations of (partly) shared underlying genetic vulnerabilities. Combined with the lack of evidence for a causal relationship from liability for ADHD to ND, these findings stress the importance to further investigate the underlying genetic vulnerability explaining co-morbidity in psychiatric disorders.

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Contains fulltext : 226694.pdf (publisher's version ) (Open Access), This systematic review is the first to provide an overview of the prospective links between food parenting practices and children's weight outcomes. Three databases were searched. All titles, abstracts and full-texts were double screened by two independent reviewers. Peer-reviewed journal articles published after 1990 assessing the prospective association between food parenting practices and weight outcomes of children aged 2-18 years were eligible. A total of 38 eligible studies were identified, focusing on 12 separate food parenting practices. Restriction, pressure to eat, and monitoring were generally not associated with children's weight over time, but higher quality studies suggest that pressure to eat was associated with lower weight outcomes over time. Most studies on food availability and accessibility found null-findings as well. Instrumental - but not emotional - feeding was associated with higher weight over time, but higher quality studies are needed to confirm this link. Results involving the link between frequency of mealtime and child weight were mixed. Autonomy supporting and other structure-related food parenting practices were understudied. In conclusion, food parenting practices receiving the most attention within prospective studies (i.e., restriction, pressure to eat, monitoring) were generally not associated with children's weight outcomes over time. Future high quality studies should focus more on other food parenting practices, further unravel bidirectional links between food parenting and children's eating behaviors and weight outcomes, and examine the mediating role of dietary intake.

Contains fulltext : 230584.pdf (Publisher’s version ) (Open Access), Risky behaviors, such as substance use and unprotected sex, are associated with various physical and mental health problems. Recent genome-wide association studies indicated that variation in the cell adhesion molecule 2 (CADM2) gene plays a role in risky behaviors and self-control. In this phenome-wide scan for risky behavior, it was tested if underlying common vulnerability could be (partly) explained by pleiotropic effects of this gene and how large the effects were. Single nucleotide polymorphism (SNP)-level and gene-level association tests within four samples (25 and Up, Spit for Science, Netherlands Twin Register, and UK Biobank and meta-analyses over all samples (combined sample of 362,018 participants) were conducted to test associations between CADM2, substance- and sex-related risk behaviors, and various measures related to self-control. We found significant associations between the CADM2 gene, various risky behaviors, and different measures of self-control. The largest effect sizes were found for cannabis use, sensation seeking, and disinhibition. Effect sizes ranged from 0.01% to 0.26% for single top SNPs and from 0.07% to 3.02% for independent top SNPs together, with sufficient power observed only in the larger samples and meta-analyses. In the largest cohort, we found indications that risk-taking proneness mediated the association between CADM2 and latent factors for lifetime smoking and regular alcohol use. This study extends earlier findings that CADM2 plays a role in risky behaviors and self-control. It also provides insight into gene-level effect sizes and demonstrates the feasibility of testing mediation. These findings present a good starting point for investigating biological etiological pathways underlying risky behaviors.

Contains fulltext : 231330.pdf (postprint version ) (Open Access), Background: The family environment plays an important role in the development of children's energy-balance related behaviors (EBRBs). As a result, parents' energy-balance parenting practices (EBRPPs) are eminent targets of preventive childhood obesity programs. Families with a lower socioeconomic position (SEP) may benefit from participating in such programs, but are generally less well reached than families with a higher SEP. Objective: This study describes the application of the Intervention Mapping Protocol (IMP) for the development of an app-based preventive intervention program to promote healthy EBRPPs among parents of children (0-4 years old) with a lower SEP. Methods: The six steps of the IMP were used as a theory- and evidence-based framework to guide the development of the app-based preventive intervention program. Results: In Step 1, behavioral outcomes for the app-based program (ie, children have a healthy dietary intake, sufficient sleep, and restricted screen time/sufficient physical activity) and socio-cognitive (ie, knowledge, attitudes, self-efficacy) and automatic (ie, habitual behaviors) determinants of energy-balance related parenting were identified through a needs assessment. In Step 2, the behavioral outcomes were translated into performance objectives. To influence these objectives, in Step 3 theory-based intervention methods were selected for each of the determinants. In Step 4, the knowledge derived from the previous steps allowed for the development of the app-based program Samen Happie! through a process of continuous co-creation with parents and health professionals. In Step 5, community health services were identified as potential adopters for the app. Lastly, in Step 6, two (randomized controlled) trials were designed to evaluate the process and effects of the app among Dutch parents of infants (Trial 1) and preschoolers (Trial 2). These trials were completed in November 2019 (Trial 1) and February 2020 (Trial 2). Conclusions: The IMP

Radboud University, 30 september 2021, Promotores : Vink, J.M., Verweij, C.J.H. Co-promotor : Abdellaoui, A., Contains fulltext : 237193.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 236270.pdf (Publisher’s version ) (Open Access), Parental stress may influence adolescents' food intake and weight development over time, however, it is largely unknown why this is the case. This study examines whether the link between parental stress and adolescents' snack intake and weight outcome is mediated by food parenting practices (FPPs). Participants included 400 parents and their adolescent children (aged 12-16) who completed questionnaires. The Perceived Stress Scale (PSS) was used to assess parental general stress levels and the Adolescent Food Parenting Questionnaire (AFPQ) to assess FPPs. Multiple mediation analyses with parallel mediators were performed, with parental general stress as an independent variable and adolescent snack intake and zBMI as dependent variables. FPPs (autonomy support, coercive control, modeling, healthy structure, snack structure) were entered as mediators in the model, adjusted for covariates. Autonomy support mediated the link between parental general stress and adolescent savory snack and sweet snack intake at follow-up. Parents who reported higher stress levels provided less autonomy support, which resulted in more adolescent snacking. None of the other FPPs mediated any link between parental stress and intake or weight outcome, and no significant indirect effects were observed with zBMI as an outcome variable. Further research should replicate this finding and may further examine underlying mechanisms.

Item does not contain fulltext, FTND (Fagerstrӧm test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported.Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND.Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND.Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

Contains fulltext : 217516.pdf (Publisher’s version ) (Closed access), Objectives: As the world population ages, psychiatrists will increasingly need instruments for measuring constructs of psychopathology that are generalizable to diverse elders. The study tested whether syndromes of co-occurring problems derived from self-ratings of psychopathology by US elders would fit self-ratings by elders in 19 other societies. Methods/design: The Older Adult Self-Report (OASR) was completed by 12 826 adults who were 60 to 102 years old in 19 societies from North and South America, Asia, and Eastern, Northern, Southern, and Western Europe, plus the United States. Individual and multigroup confirmatory factor analyses (CFAs) tested the fit of the seven-syndrome OASR model, consisting of the Anxious/Depressed, Worries, Somatic Complaints, Functional Impairment, Memory/Cognition Problems, Thought Problems, and Irritable/Disinhibited syndromes. Results: In individual CFAs, the primary model fit index showed good fit for all societies, while the secondary model fit indices showed acceptable to good fit. The items loaded strongly on their respective factors, with a median item loading of .63 across 20 societies, and 98.7% of the loadings were statistically significant. In multigroup CFAs, 98% of items demonstrated approximate or full metric invariance. Fifteen percent of items demonstrated approximate or full scalar invariance, and another 59% demonstrated scalar invariance across more than half of societies. Conclusions: The findings supported the generalizability of OASR syndromes across societies. The seven syndromes offer empirically based clinical constructs that are relevant for elders of different backgrounds. They can be used to assess diverse elders and as a taxonomic framework to facilitate communication, services, research, and training in geriatric psychiatry.

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Contains fulltext : 226491.pdf (publisher's version ) (Open Access)

Contains fulltext : 219151.pdf (Publisher’s version ) (Closed access), Objective: Ecstasy is one of the most commonly used illicit substances in Western countries. The aim of this study is to identify characteristics of ecstasy users in a large population-based sample of adults aged 18-45 years. Method: With generalized estimating equation models we explored the association between self-reported lifetime ecstasy use and urbanicity, educational attainment, health, wellbeing, stress, other substance use, personality traits and psychopathology in a Dutch twin sample (N=9,578, 66.8% female, 18-45 years). We also explored the nature of the association (underlying genetic factors, shared environmental factors or a causal relationship) with the co-twin control method. Results: Lifetime ecstasy users (N=945, 9.9%) were more often male, younger, living more often in urban areas, higher educated, less satisfied with life and more stressed than non-users. Ecstasy users scored differently on most personality and psychopathology scales compared to non-users and were more likely to have used every other substance we investigated. Whereas smoking tobacco and alcohol use often preceded first use of ecstasy, first ecstasy use often preceded first use of other illicit substances. A combination of scenarios (both causal and environmental/genetic) explained the strong associations between ecstasy and substance use. For the other variables no causal association was likely but genetic factors (i.e. psychopathology), shared environmental factors (i.e. demographics) or no clear pattern (i.e. personality) were likely scenarios. Conclusions: Ecstasy users differ on many characteristics from non-users, and especially on illicit substance use. In addition, our results indicate that causal effects may play a role in explaining the relationship between ecstasy use and other illicit substance use.

Contains fulltext : 220283.pdf (publisher's version ) (Open Access), Background: Poor sleep quality and insomnia have been associated with the use of tobacco, alcohol, and cannabis, but it is unclear if there is a causal link. In this Mendelian Randomization (MR) study we examine if insomnia causes substance use and/or if substance use causes insomnia. Methods: MR uses summary effect estimates from a genome-wide association study (GWAS) to create a genetic instrumental variable for a proposed 'exposure' variable and then identifies that same genetic instrument in an 'outcome' GWAS. Using GWASs of insomnia, smoking (initiation, heaviness, cessation), alcohol use (drinks per week, dependence), and cannabis initiation, bi-directional causal effects were tested. Multiple sensitivity analyses were applied to assess the robustness of the findings. Results: There was strong evidence for positive causal effects of liability to insomnia on all substance use phenotypes (smoking traits, alcohol dependence, cannabis initiation), except alcohol per week. In the other direction, there was strong evidence that smoking initiation increased insomnia risk (smoking heaviness and cessation could not be tested as exposures). We found no evidence that alcohol use per week, alcohol dependence, or cannabis initiation causally affect insomnia risk. Conclusions: There were unidirectional effects of liability to insomnia on alcohol dependence and cannabis initiation, and bidirectional effects between liability to insomnia and smoking measures. Bidirectional effects between smoking and insomnia might give rise to a vicious circle. Future research should investigate if interventions aimed at insomnia are beneficial for substance use treatment.

Contains fulltext : 217711.pdf (Publisher’s version ) (Closed access), Background: Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide association study (GWAS) summary statistics from the UK Biobank, International Cannabis Consortium, and GWAS & Sequencing Consortium of Alcohol and Nicotine use. Methods: We obtained GWAS summary statistics from the aforementioned consortia for ten substance use traits including various measures of alcohol consumption, caffeine consumption, cannabis initiation and smoking behaviours. We then conducted SNP-heritability (h2) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs. Results: SNP h2 of the ten traits ranged from 0.03 to 0.11. After multiple testing correction, 29 of the 45 trait pairs showed evidence of being genetically correlated. MR analyses revealed that most SU traits were not causally associated with each other. However, we found evidence for an MR association between regular smoking initiation and caffeine consumption 40.17 mg; 95% CI: [ 24.01, 56.33] increase in caffeine intake per doubling of odds in smoking initiation). Our findings were robust against horizontal pleiotropy, SNP-outliers, and the direction of causality was consistent in all MR analyses. Conclusions: Most of the substance traits were genetically correlated but there is little evidence to establish causality apart from the relationship between smoking initiation and caffeine consumption.

Contains fulltext : 217211.pdf (publisher's version ) (Open Access), Both mothers' and best friends' food intake are associated with adolescents' food intake, but they are rarely investigated simultaneously. In this study, we tested the associations of mothers' and best friends’ food intake with adolescents' intake of unhealthy and healthy food, obtained from home and from outside the home, and the moderating role of adolescents' exposure to their food intake. Participants included 667 adolescents (53% female, Mage = 12.9) and 396 of their mothers. Within this adolescent sample, 378 best friend dyads were identified. All participants completed food frequency questionnaires. Mothers separately reported on their food intake in the presence and absence of their child, and adolescents indicated how often they ate and drank together with their best friend during school breaks. Mothers', but not best friends', food intake was positively related to adolescents' intake of unhealthy and healthy food obtained from home and healthy food obtained from outside the home. Exposure to mothers' healthy food intake magnified mother-child similarities in healthy food intake. Exposure to best friends' intake of unhealthy food moderated adolescent-friend similarities in unhealthy food intake. Future work should assess the mechanisms that underlie these similarities, and should investigate these associations over time and in later developmental periods.

Contains fulltext : 216912.pdf (publisher's version ) (Open Access), Background: Tobacco, alcohol, and cannabis use are prevalent behaviors that pose considerable health risks. Genetic vulnerability and characteristics of the neighborhood of residence form important risk factors for substance use. Possibly, these factors do not act in isolation. This study tested the interaction between neighborhood characteristics and genetic risk (gene-environment interaction, GxE) and the association between these classes of risk factors (gene-environment correlation, rGE) in substance use. Methods: Two polygenic scores (PGS) each (based on different discovery datasets) were created for smoking initiation, cigarettes per day, and glasses of alcohol per week based on summary statistics of different genome-wide association studies (GWAS). For cannabis initiation one PGS was created. These PGS were used to predict their respective phenotype in a large population-based sample from the Netherlands Twin Register (N = 6,567). Neighborhood characteristics as retrieved from governmental registration systems were factor analyzed and resulting measures of socioeconomic status (SES) and metropolitanism were used as predictors. Results: There were (small) main effects of neighborhood characteristics and PGS on substance use. One of the 14 tested GxE effects was significant, such that the PGS was more strongly associated with alcohol use in individuals with high SES. This was effect was only significant for one out of two PGS. There were weak indications of rGE, mainly with age and cohort covariates. Conclusion: We conclude that both genetic and neighborhood-level factors are predictors for substance use. More research is needed to establish the robustness of the findings on the interplay between these factors.

Contains fulltext : 216593.pdf (publisher's version ) (Open Access), Not much is known regarding underlying biological pathways to adolescents' loneliness. Insight in underlying molecular mechanisms could inform intervention efforts aimed at reducing loneliness. Using latent growth curve modeling, baseline levels and development of loneliness were studied in two longitudinal adolescent samples. Genes (OXTR, OXT, AVPR1A, AVPR1B) were examined using SNP-based, gene-based, and polygenic risk score (PRS) approaches. In both samples, SNP- and gene-based tests showed involvement of the OXTR gene in development of loneliness, though, significance levels did not survive correction for multiple testing. The PRS approach provided no evidence for relations with loneliness. We recommend alternative phenotyping methods, including environmental factors, to consider epigenetic studies, and to examine possible endophenotypes in relation to adolescents' loneliness.

Contains fulltext : 221836.pdf (publisher's version ) (Open Access), 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.

Contains fulltext : 219447.pdf (Publisher’s version ) (Closed access), Attention-deficit/hyperactivity disorder (ADHD) is a severely impairing neurodevelopmental disorder with a prevalence of 5% in children and adolescents and of 2.5% in adults. Comorbid conditions in ADHD play a key role in symptom progression, disorder course and outcome. ADHD is associated with a significantly increased risk for substance use, abuse and dependence. ADHD and cannabis use are partly determined by genetic factors; the heritability of ADHD is estimated at 70-80% and of cannabis use initiation at 40-48%. In this study, we used summary statistics from the largest available meta-analyses of genome-wide association studies (GWAS) of ADHD (n = 53,293) and lifetime cannabis use (n = 32,330) to gain insights into the genetic overlap and causal relationship of these two traits. We estimated their genetic correlation to be r2 = 0.29 (P = 1.63 x 10-5) and identified four new genome-wide significant loci in a cross-trait analysis: two in a single variant association analysis (rs145108385, P = 3.30 x 10-8 and rs4259397, P = 4.52 x 10-8) and two in a gene-based association analysis (WDPCP, P = 9.67 x 10-7 and ZNF251, P = 1.62 x 10-6). Using a two-sample Mendelian randomization approach we found support that ADHD is causal for lifetime cannabis use, with an odds ratio of 7.9 for cannabis use in individuals with ADHD in comparison to individuals without ADHD (95% CI (3.72, 15.51), P = 5.88 x 10-5). These results substantiate the temporal relationship between ADHD and future cannabis use and reinforce the need to consider substance misuse in the context of ADHD in clinical interventions.

Contains fulltext : 219581.pdf (publisher's version ) (Open Access), Background: The use of illicit substances is correlated, meaning that individuals who use one illicit substance are more likely to also use another illicit substance. This association could (partly) be explained by overlapping genetic factors. Genetic overlap may indicate a common underlying genetic predisposition, or can be the result of a causal association. Methods: Polygenic scores for lifetime cannabis use were generated in a sample of Dutch participants (N = 8348). We tested the association of a PGS for cannabis use with ecstasy, stimulants and a broad category of illicit drug use. To explore the nature of the relationship: (1) these analyses were repeated separately in cannabis users and non-users and (2) monozogytic twin pairs discordant for cannabis use were compared on their drug use. Results: The lifetime prevalence was 24.8% for cannabis, 6.2% for ecstasy, 6.5% for stimulants and 7.1% for any illicit drug use. Significant, positive associations were found between PGS for cannabis use with ecstasy use, stimulants and any illicit drug use. These associations seemed to be stronger in cannabis users compared to non-users for both ecstasy and stimulant use, but only in people born after 1968 and not significant after correction for multiple testing. The discordant twin pair analyses suggested that cannabis use could play a causal role in drug use. Conclusions: The genetic liability underlying cannabis use significantly explained variability in ecstasy, stimulant and any illicit drug use. Further research should further explore the underlying mechanism to understand the nature of the association.

Contains fulltext : 216629.pdf (publisher's version ) (Open Access), Background: Little is known about the functional mechanisms through which genetic loci associated with substance use traits ascertain their effect. This study aims to identify and functionally annotate loci associated with substance use traits based on their role in genetic regulation of gene expression. Methods: We evaluated expression Quantitative Trait Loci (eQTLs) from 13 brain regions and whole blood of the Genotype-Tissue Expression (GTEx) database, and from whole blood of the Depression Genes and Networks (DGN) database. The role of single eQTLs was examined for six substance use traits: alcohol consumption (N = 537,349), cigarettes per day (CPD; N = 263,954), former vs. current smoker (N = 312,821), age of smoking initiation (N = 262,990), ever smoker (N = 632,802), and cocaine dependence (N = 4,769). Subsequently, we conducted a gene level analysis of gene expression on these substance use traits using S-PrediXcan. Results: Using an FDR-adjusted p-value < 0.05 we found 2,976 novel candidate genetic loci for substance use traits, and identified genes and tissues through which these loci potentially exert their effects. Using S-PrediXcan, we identified significantly associated genes for all substance traits. Discussion: Annotating genes based on transcriptomic regulation improves the identification and functional characterization of candidate loci and genes for substance use traits.