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AbstractEtiological factors for stability and change in symptoms of anxiety and depression, including sex differences, are largely unexplored in young adults. Using biometric modeling and two-wave longitudinal data from 4393 Norwegian twins aged 18 to 31 we explored (i) heritabilities of symptoms of anxiety and depression, (ii) effects of genetic and environmental factors on the stability and change of such symptoms, and (iii) sex-specific effects. The phenotypic cross-time correlations for symptoms of anxiety and depression were estimated to .54 and .49 for males and females, respectively. The best fitting longitudinal model specified additive genetic and individual environmental influences and emerging effects from the shared environment for females only. For both males and females, long-term stability was mainly attributable to stable additive genetic factors, whereas change was essentially related to environmental influences. Minor time-specific genetic effects were indicated, and some stable variance was due to the individual environment. Additive genetic risk factors explained 87% and 68% of the phenotypic cross-time correlation for males and females, with the unique environment accounting for the remaining covariance. The results provide strong evidence for the temporal stability of genetic risk factors for symptoms of anxiety and depression in young adults, and substantial sex-specific influences on heritability, stability and change.

AbstractThe relationship between subjective wellbeing (SWB) and self-reported sleep problems was investigated in a cohort of Norwegian twins aged 18 to 31 years. Questionnaire data from 8045 same- and opposite-sex twins were analyzed using structural equation modeling to explore the relative effects of genetic and environmental influences on phenotypic variance and covariance. Special attention was paid to sex-specific effects. The correlation between the phenotypes was estimated to be −.43. Univariate analyses indicated considerable genetic influences for both SWB and sleep problems, for male and female twins alike. The best fitting bivariate model specified additive genetic and individual environmental factors for both phenotypes, and nonadditive genetic effects for sleep problems, with no sex-specific effects. Genetic and environmental effects accounted for 60% and 40% of the phenotypic correlation, respectively. Additive genetic factors affecting the two phenotypes were correlated (−.85), suggesting that part of the genetic effects that positively influence SWB also protect against sleep problems. In conclusion, the results indicate considerable overlap in genetic etiology for SWB and sleep problems, for males and females alike.

AbstractWhile snus has been the focus of increasing public health interest, twin studies have examined neither sources of individual variation for its use nor the sources of resemblance between snus and cigarette use. Twins from the Norwegian Institute of Public Health Panel were assessed by self-report questionnaire for the initiation of regular use and maximal quantity used for snus and cigarettes. Twin modeling was performed using OpenMx on data from 2767 twins including 856 complete pairs. Fitting univariate twin models produced similar results for cigarette initiation and quantity with estimates of additive genetic, shared environmental and unique environmental effects of approximately 77%, 0% and 23%, respectively. Estimates of snus initiation and quantity were, respectively, approximately 53%, 26% and 21%. Joint analyses suggested that the genetic, shared environmental and unique environmental correlations between cigarette and snus initiation and quantity were +.82, 0 and +.42, respectively. However, these results could not be statistically distinguished from a model which postulated that resemblance between cigarette initiation and quantity resulted from genetic and unique environmental correlations of +.47 and +.43. Compared with cigarette initiation and quantity of use in Norwegian twins, the role of genes was less prominent and shared environment more prominent for initiation and quantity of use of snus. Joint analyses of both tobacco phenotypes suggested, but did not confirm definitively, that genetic risk factors for cigarette and snus use were similar but not identical, while shared environmental factors existed that were specific to snus use.

In many Western countries, women now reach educational levels comparable to men, although their income remains considerably lower. For the past decades, it has become increasingly clear that these measures of socio-economic status are influenced by genetic as well as environmental factors. Less is known about the relationship between education and income, and sex differences. The aim of this study was to explore genetic and environmental factors influencing education and income in a large cohort of young Norwegian twins, with special emphasis on gender differences. National register data on educational level and income were obtained for 7,710 twins (aged 29–41 years). Bivariate Cholesky models were applied to estimate qualitative and quantitative gender differences in genetic and environmental influences, the relative contribution of genetic and environmental factors to the correlation between education and income, and genetic correlations within and between sexes and phenotypes. The phenotypic correlation between educational level and income was 0.34 (0.32–0.39) for men and 0.45 (0.43–0.48) for women. An ACE model with both qualitative and quantitative sex differences fitted the data best. The genetic correlation between men and women (rg) was 0.66 (0.22–1.00) for educational attainment and 0.38 (0.01–0.75) for income, and between the two phenotypes 0.31 (0.08–0.52) for men and 0.72 (0.64–0.85) for women. Our results imply that, in relatively egalitarian societies with state-supported access to higher education and political awareness of gender equality, genetic factors may play an important role in explaining sex differences in the relationship between education and income.

Objective: Posttraumatic stress disorder (PTSD) is one of the only disorders in the Diagnostic and Statistical Manual of Mental Disorders that requires an environmental exposure. The relationship between liability factors for trauma exposure and those for PTSD symptoms following exposure are unclear. Methods: Exposure to a trauma and resulting PTSD symptoms were assessed in a sample of 2,794 members of the Norwegian Institute of Public Health Twin Panel. Results: In the full sample, 737 twins experienced a trauma. A modified causal, contingent, common pathway model was used to examine trauma exposure and liability for PTSD. Genetic and common environmental factors could not be distinguished, so a model that included only familial and individual specific components was fit. The best-fitting model suggested that familial factors played an important role in liability for trauma exposure and for resulting PTSD symptoms, and that there was a modest transmission between trauma exposure and subsequent PTSD symptoms. Conclusions: One third of the variance in liability of PTSD symptoms is due to familial factors, and of this, approximately one fifth overlaps with the familial liability for trauma exposure while the other four fifths of the variance is specific to the risk of PTSD symptoms following exposure. The hypothesis that PTSD is etiologically similar to exposures to a traumatic event is not supported, suggesting that the factors that confer risk for trauma do not overlap completely with those that confer risk for PTSD.

AbstractAll Norwegian twin pairs born 1967–1974 and still living in Norway in 1992 were invited to a health questionnaire study (Q1). 2,570 pairs (65%) participated. These cohorts and the twin cohorts born 1967–1979 were invited to a new questionnaire study (Q2) in 1998. This time 3,334 pairs (53%) participated. Almost all pairs having participated in the 1998 study were invited to an interview study of mental health (MHS), taking place 1999–2004. 1,391 complete pairs (44%) participated. The questionnaire studies included extensive data on somatic health with fewer items on mental health and demography. Health-related and demographic information available from the Medical Birth Registry on all invited twins was applied to predict participation to the first study. A few registry variables indicating poor health predicted nonparticipation in Q1. Health information and demography from Q1 were tested as predictors of participation in the follow-up study (Q2). Monozygosity, female sex, being unmarried, having no children, and high education predicted participation, whereas few indicators of poor mental and somatic health and unhealthy lifestyle moderately predicted nonparticipation in Q2. No health indicators reported in Q2 predicted further participation. Standard genetic twin analyses of indicators of various mental disorders from Q2, validated by diagnostic data from the MHS, did not indicate differences in genetic/environmental covariance structures between participants and nonparticipants in MHS. In general the results show a moderate selection towards good mental and somatic health. Attrition from Q2 to the MHS does not appear to affect twin analyses of mental health related variables.

Self-report scales for symptoms of anxiety and depression are frequently used for screening and research purposes. A moderate phenotypic association between disorders measured by diagnostic interviews and symptoms of anxiety and depression measured by self-report scales has been shown, but little is known about the overlap in these phenotypes' genetic and environmental variance. In the present study, we used twin modeling to identify common genetic and environmental liabilities underlying the phenotypic association between the self-report Symptom Checklist-5 (SCL-5) and lifetime internalizing disorders derived from the Composite International Diagnostic Interview (CIDI). The sample consisted of 7,992 young adult twins from the Norwegian Institute of Public Health Twin Panel (NIPHT), who all responded to a questionnaire. A subset of 2,793 individuals later underwent structured interviews. The best fitting model showed a strong genetic correlation of 0.82 (95% confidence interval; 0.61–1.0) between current self-report symptoms of anxiety and depression, and lifetime internalizing disorders, which suggests an almost complete overlap in genetic liability. The correlation between environmental factors was much lower: 0.16 (0.00–0.34, 95% CI). This implies that brief self-report scales capture genetic variance that is highly overlapping with the genetic variance common to internalizing disorder diagnoses. It thus follows that SCL-5 and similar instruments may be used as screening instruments for genetic risk factors that influence liability to internalizing disorders. In addition, existing data on self-report symptoms of anxiety and depression can be used with increased confidence to specify models including effects from genes coding for internalizing disorders.

AbstractWork incapacity is a major public health challenge and an economic burden to both society and individuals. Understanding the underlying causes is becoming ever more relevant as many countries face an aging workforce. We examined stability and change in genetic and environmental factors influencing work incapacity from age 18 until retirement, and sex differences in these effects. The large population-based sample comprised information from 28,759 twins followed for up to 23 years combined with high-quality national registry data. We measured work incapacity as the total proportion of potential workdays lost due to sickness absence, rehabilitation and disability benefits. Structural equation modeling with twin data indicated moderate genetic influences on work incapacity throughout life in both men and women, with a high degree of genetic stability from young to old adulthood. Environmental influences were mainly age-specific. Our results indicate that largely the same genetic factors influence individual differences in work incapacity throughout young, middle and older adulthood, despite major differences in degree of work incapacity and probable underlying medical causes.

Personality disorders (PDs) reduce global functioning, are associated with high levels of work disability, and are thus also likely to influence long-term sick leave (LTSL). Previous research has indicated significant genetic influence on both DSM-IV PDs and LTSL. To what degree genes contributing to PDs also influence LTSL has not been investigated. The aims of the current study were to investigate which PDs were significantly associated with LTSL, to what extent the genetic contributions to these PDs account for the heritability of LTSL, and to explore the hypothesis of a causal association between PDs and LTSL. The sample consisted of 2,771 young, adult Norwegian twins, born 1967–1979. PDs were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV). The age range for the interview was 20–32. The data were subsequently linked to public records of LTSL (sick leave >16 days) up to 11 years later. The odds ratio for being in the highest LTSL category (>15% sick leave) when fulfilling the DSM-IV criteria for any PD diagnosis was 2.6 (1.8–3.8, 95% CI). Dimensional representations of schizotypal, paranoid, and borderline PD were independently and significantly associated with LTSL. The heritability of LTSL was 0.50. Genetic factors shared with the PDs accounted for 20% of this. The association between PDs and LTSL was due to shared genetic and not environmental influences, and was mainly explained by one common genetic factor. The hypothesis of a causal association was not supported, indicating that the association is explained by overlapping genetic liability between PDs and LTSL.

This study investigates the degree to which internalizing disorders (anxiety and mood disorders) are prospectively associated with sick leave granted for mental and somatic disorders, and the extent to which common genetic and environmental risk factors influence these relationships. Data include self-reported symptoms of psychological distress from 7,598 young adult twins and diagnostic interviews on a subsample of 2,766 adult twins, subsequently linked to registry data on sick leave. Regression analyses and multivariate twin models were used to investigate the relationship between internalizing disorders and sick leave. Internalizing disorders were associated with sick leave granted for both mental disorders and somatic disorders. The association between internalizing disorders and sick leave granted for mental disorders was influenced by genetic and non-shared environmental factors, while the association between internalizing disorders and sick leave granted for somatic disorders could be explained by common genetic factors alone. Monozygotic twins discordant for internalizing disorders differed significantly in rates of sick leave granted for mental but not somatic disorders. In conclusion, internalizing disorders in young adults predict sick leave granted for both mental and somatic disorders. Environmental risk factors for internalizing disorders seem to influence sick leave granted for mental disorders, but not sick leave granted for somatic disorders.

Although exclusion from the workforce due to long-term sick leave (LTSL) and disability pension (DP) is a major problem in many Western countries, the etiology of LTSL and DP is not well understood. These phenomena have a strong association as most patients receiving DP have first been on LTSL. However, only a few of those on LTSL end up with DP. The present study aimed to investigate the common and specific genetic and environmental risk factors for LTSL and DP. The present study utilizes a population-based sample of 7,710 young adult twins from the Norwegian Institute of Public Health Twin Panel, which has been linked to the Historical-Event Database (FD-Trygd; 1998–2008). Univariate and bivariate twin models were fitted to determine to what degree genetic and environmental factors contribute to variation in LTSL and DP. The estimated heritabilities of LTSL and DP were 0.49 and 0.66, respectively. There was no evidence for shared environmental or sex-specific factors. The phenotypic-, genetic-, and non-familial environmental correlations between the variables were 0.86, 0.82, and 0.94, respectively. Our results indicate that familial transmission of LTSL and DP is due to genetic and not environmental factors. The risk factors contributing to LTSL and DP were mainly shared, suggesting that what increases risk for LTSL also increases risk for DP. However, a non-negligible part of the genetic variance was not shared between the variables, which may contribute to explaining why some progress from LTSL to DP, whereas others return to work.

We describe the importance of the Norwegian Twin Registry (NTR) for research in public health and provide examples from several programs of twin research at the Norwegian Institute of Public Health (NIPH), including the Nordic Twin Study of Cancer, our epigenetics platform, and our large program of research in mental health. The NTR has become an integral component of a national strategy for maximizing the research potential from Norwegian registries and biobank-based studies. The information provided herein builds upon and complements our recent report describing the establishment of the NTR and the cohorts comprising it. Although Norway has a long tradition in twin research, the centralization and administration of the twin data through a single register structure is fairly recent. The NTR was established in 2009 and currently includes 47,989 twins covering birth years 1895–1960 and 1967–1979; 31,440 of these twins have consented to participate in medical research (comprising 5,439 monozygotic pairs, 6,702 dizygotic same-sexed pairs, and 1,655 dizygotic opposite-sexed pairs). DNA from approximately 4,800 twins is banked at the NIPH biobank and new studies continuously add new data to the registry. The value of NTR data is greatly enhanced through record linkage possibilities offered by Norway's many nation-wide registries (medical, demographic, and socio-economic) and several studies are already taking advantage of these linkage opportunities for research.

Until now, data have not been available to elucidate the genetic and environmental sources of comorbidity between all 10 DSM-IV personality disorders (PDs) and cocaine use. Our aim was to determine which PD traits are linked phenotypically and genetically to cocaine use. Cross-sectional data were obtained in a face-to-face interview between 1999 and 2004. Subjects were 1,419 twins (µage = 28.2 years, range = 19–36) from the Norwegian Institute of Public Health Twin Panel, with complete lifetime cocaine use and criteria for all 10 DSM-IV PDs. Stepwise multiple and Least Absolute Shrinkage and Selection Operator (LASSO) regressions were used to identify PDs related to cocaine use. Twin models were fitted to estimate genetic and environmental associations between the PD traits and cocaine use. In the multiple regression, antisocial (OR = 4.24, 95% CI [2.66, 6.86]) and borderline (OR = 2.19, 95% CI [1.35, 3.57]) PD traits were significant predictors of cocaine use. In the LASSO regression, antisocial, borderline, and histrionic were significant predictors of cocaine use. Antisocial and borderline PD traits each explained 72% and 25% of the total genetic risks in cocaine use, respectively. Genetic risks in histrionic PD were not significantly related to cocaine use. Importantly, after removing criteria referencing substance use, antisocial PD explained 65% of the total genetic variance in cocaine use, whereas borderline explained only 4%. Among PD traits, antisocial is the strongest correlate of cocaine use, for which the association is driven largely by common genetic risks.

Publisher's version (útgefin grein). ; Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities. ; We are grateful to the participants and we thank the staff at the Research Recruitment Center. We also thank the staff at deCODE genetics core facilities and all our colleagues for their important contribution to this work. We are grateful to the Benefit Society for Children with Disabilities (Styrktarfélag Lamaðra og Fatlaðra; SLF) for their participation. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreements' no. 115008 (NEWMEDS) and no. 115300 (EUAIMS), of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (EU-FP7/2007–2013), from EU-FP7 grants no. 602450 (IMAGEMEND) and no. 502805 (Aggressotype), EU-FP7-People-2011-IAPP grant no. 286213 (PsychDPC), and The Research Council of Norway (#226971, 229129, 223273, 213694, 248778), the KG Jebsen Stiftelsen (SKGJ-MED-002 and SKGJ-MED-008), and The South-East Norway Health Authority (#2012–132). ; Peer Reviewed

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5-BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10-21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities. ; Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Programme (EU-FP7/2007-2013) European Union (EU) EU-FP7-People-2011-IAPP grant Research Council of Norway KG Jebsen Stiftelsen South-East Norway Health Authority