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This study uses novel approaches to examine genetic and environmental influences shared between childhood behavioral inhibition (BI) and symptoms of preadolescent anxiety disorders. Three hundred and fifty-two twin pairs aged 9-13 and their mothers completed questionnaires about BI and anxiety symptoms. Biometrical twin modeling, including a direction-of-causation design, investigated genetic and environmental risk factors shared between BI and social, generalized, panic and separation anxiety. Social anxiety shared the greatest proportion of genetic (20%) and environmental (16%) variance with BI with tentative evidence for causality. Etiological factors underlying BI explained little of the risk associated with the other anxiety domains. Findings further clarify etiologic pathways between BI and anxiety disorder domains in children. [ABSTRACT FROM AUTHOR]

Schooling differences between identical twins are often utilized as a natural experiment to estimate returns to education. Despite longstanding doubts about the truly random nature of within-twin-pair schooling discordance, such discordance has not yet been understood comprehensively, in terms of diverse between- and within-family peer, academic, familial, social, and health exposures. Here, a predictive analysis using national U.S. midlife twin data shows that within-pair schooling differences are endogenous to a variety of childhood exposures. Using discordance propensities, returns to education under a true natural experiment are simulated. Results for midlife occupation and income reveal differences in estimated returns to education that are statistically insignificant, suggesting that twin-based estimates of causal effects are robust. Moreover, identical and fraternal twins show similar levels of discordance endogeneity and similar responses to propensity weighting, suggesting that the identical twins may not provide demonstrably better leverage in the causal identification of educational returns. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Avera Twin Register (ATR) aims to study environmental and genetic influences on health and disease using a longitudinal repository of biological specimens, survey data, and health information provided by multiples and their family members. The ATR is located in Sioux Falls, South Dakota, which is a rural and frontier area in the Midwestern United States with a density of four people per square kilometer. The target area of the ATR is South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota, and Nebraska. Enrollment of twins and higher-order multiples of all ages and their family members started on May 18, 2016. A description of the first 13 months of enrollment in this longitudinal register will be provided. The ATR will collect longitudinal data on lifestyle, including diet and activity levels, aging, complex traits, and diseases. Upon registration, all participants are genotyped on the Illumina Global Screening Array (GSA) and twins and higher order multiples receive information on their zygosity. The ATR aims to contribute to large international GWAS consortia and collaborates closely with the Netherlands Twin Register, allowing for the comparison of collected data and analyses of results. In addition, the ATR will address twin-specific questions. [ABSTRACT FROM AUTHOR]

Genetic and environmental factors contribute to the etiology of anorexia nervosa (AN). The co-twin control design is one of the most powerful methods available to evaluate environmental factors that could contribute to differences between monozygotic (MZ) twins who are discordant for AN. Using available data from a unique and rare sample of 22 Swedish female MZ pairs discordant for AN, we compared personality, life events, comorbidity, and health factors. Twins with AN had significantly higher perfectionism scores than unaffected co-twins and reported younger ages at first diet than unaffected co-twins who had dieted. Consistent with previous literature, more twins with AN reported gastrointestinal problems than unaffected co-twins. Although not significant due to low statistical power, more unaffected co-twins reported experiencing emotional neglect than twins with AN. Early dieting may be a harbinger of the development of AN or an early symptom. Higher perfectionism may represent a risk factor, sequela, or both. Sibling perception of neglect is noteworthy given the impact of an ill child with AN on family function and wellbeing. The health and wellbeing of siblings should be addressed clinically when one child in the family suffers from AN. [ABSTRACT FROM PUBLISHER]

Background: Despite evidence for some genetic control of dietary intake in adults, there is little evidence of how genetic factors influence children's dietary patterns.Objective: To estimate heritability of dietary intake in twin children from China and test if genetic effects on dietary intakes vary by the children's socio-economic status (SES).Methods: A sample of 622 twins (162 monozygotic and 149 dizygotic pairs; 298 boys and 324 girls aged 7-15 years) was recruited in South China. Dietary intakes were assessed using a validated 145-item semi-quantitative food frequency questionnaire. Pooled and sex-specific dietary patterns were identified using factor analysis. Heritability was estimated using structural equation models.Results: Heritable components differed by gender and for nutrients and food groups; and estimated heritability of dietary patterns was generally greater in girls than boys. In boys, estimated heritabilities ranged from 18.8% (zinc) to 58.4% (fat) for nutrients; and for food group, 1.1% (Western fast foods) to 65.8% (soft drinks). In girls, these estimates ranged from 5.1% (total energy) to 38.7% (percentage of energy from fat) for nutrients, and 12.6% (eggs) to 94.6% (Western fast foods) for food groups. Factor analysis identified five food patterns: vegetables and fruits, fried and fast foods, beverages, snacks and meats. Maternal education and family income were positively associated with higher heritabilities for intake of meat, fried, and fast food.Conclusions: Genetic influence on dietary intakes differed by gender, nutrients, food groups, and dietary patterns among Chinese twins. Parental SES characteristics modified the estimated genetic influence. [ABSTRACT FROM AUTHOR]

Avoiding overeating and being physically active is associated with healthy aging, but methodological issues challenge the quantification of the association. Intrapair comparison of twins is a study design that attempts to minimize social norm-driven biased self-reporting of lifestyle factors. We aimed to investigate the association between self-reported lifestyle factors and subsequent survival in 347 Danish twin pairs aged 70 years and older and, additionally, to investigate the reliability of these self-reports. The twins were interviewed in 2003 and followed for mortality until 2015. They were asked to compare their appetite and physical activity to that of their co-twins in different stages of life. On an individual level, we found a positive association between current self-reported physical activity and late-life survival for elderly twins. This was supported by the intrapair analyses, which revealed a positive association between midlife and current physical activity and late-life survival. A positive association between lower appetite and late-life survival was found generally over the life course in the individual level analyses but not in the intrapair analyses. Kappa values for the inter-twin agreement on who ate the most were 0.16 to 0.34 in different life stages, and for physical activity 0.19 to 0.26, corresponding to a slight-to-fair agreement. Approximately, 50% of the twin pairs were not in agreement regarding physical activity, and of these twins 75% (95% CI: 67–82%) considered themselves the most active twin. These findings indicate a still-existing tendency of answering according to social norms, even in a twin study designed to minimize this. [ABSTRACT FROM PUBLISHER]

Objectives: This research examined the familial aggregation of migraine, depression, and their co-occurrence.Methods: Diagnoses of migraine and depression were determined in a sample of 5,319 Australian twins. Migraine was diagnosed by either self-report, the ID migraine™ Screener, or International Headache Society (IHS) criteria. Depression was defined by fulfilling either major depressive disorder (MDD) or minor depressive disorder (MiDD) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. The relative risks (RR) for migraine and depression were estimated in co-twins of twin probands reporting migraine or depression to evaluate their familial aggregation and co-occurrence.Results: An increased RR of both migraine and depression in co-twins of probands with the same trait was observed, with significantly higher estimates within monozygotic (MZ) twin pairs compared to dizygotic (DZ) twin pairs. For cross-trait analysis, the RR for migraine in co-twins of probands reporting depression was 1.36 (95% CI: 1.24–1.48) in MZ pairs and 1.04 (95% CI: 0.95–1.14) in DZ pairs; and the RR for depression in co-twins of probands reporting migraine was 1.26 (95% CI: 1.14–1.38) in MZ pairs and 1.02 (95% CI: 0.94–1.11) in DZ pairs. The RR for strict IHS migraine in co-twins of probands reporting MDD was 2.23 (95% CI: 1.81–2.75) in MZ pairs and 1.55 (95% CI: 1.34–1.79) in DZ pairs; and the RR for MDD in co-twins of probands reporting IHS migraine was 1.35 (95% CI: 1.13–1.62) in MZ pairs and 1.06 (95% CI: 0.93–1.22) in DZ pairs.Conclusions: We observed significant evidence for a genetic contribution to familial aggregation of migraine and depression. Our findings suggest a bi-directional association between migraine and depression, with an increased risk for depression in relatives of probands reporting migraine, and vice versa. However, the observed risk for migraine in relatives of probands reporting depression was considerably higher than the reverse. These results add further support to previous studies suggesting that patients with comorbid migraine and depression are genetically more similar to patients with only depression than patients with only migraine. [ABSTRACT FROM PUBLISHER]

Studies have suggested both adverse and protective associations of obesity with depressive symptoms. We examined the contribution of environmental and heritable factors in this association. Participants were same-sex twin pairs from two population-based twin cohort studies, the Older Finnish Twin Cohort (n = 8,215; mean age = 44.1) and the US Midlife Development in the United States (MIDUS; n = 1,105; mean age = 45.1). Body mass index (BMI) was calculated from self-reported height and weight. Depressive symptoms were assessed using Beck's Depression Inventory (BDI; Finnish Twin Cohort), and by negative and positive affect scales (MIDUS). In the Finnish Twin Cohort, higher BMI was associated with higher depressive symptoms in monozygotic (MZ) twins (B = 2.01, 95% CI = 1.0, 3.0) and dizygotic (DZ) twins (B = 1.17, 0.5, 1.9) with BMI >22. This association was observed in within-pair analysis in DZ twins (B = 1.47, CI = 0.4, 2.6) but not in within-pair analysis of MZ twins (B = 0.03, CI = -1.9, 2.0). Consistent with the latter result, a bivariate genetic model indicated that the association between higher BMI and higher depressive symptoms was largely mediated by genetic factors. The results of twin-pair analysis and bivariate genetic model were replicated in the MIDUS sample. These findings suggest an association between obesity and higher depressive symptoms, which is largely explained by shared heritable biological mechanisms. [ABSTRACT FROM AUTHOR]

Background: Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder.Aims: To quantify the shared genetic variability between bipolar disorder and cognitive measures.Method: Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder.Results: Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|-|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|-|1.00|), which remained significant after covarying for affective symptoms.Conclusions: Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder. [ABSTRACT FROM AUTHOR]

Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in ‘frequency of internet use’ was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in ‘frequency of use after 11 pm’, ‘using the internet to contact peers’, and ‘using the internet primarily to access social networking sites’ was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between ‘frequency of internet use’ and ‘frequency of use after 11 pm’ with social phobia (SP). ‘Using the internet to contact peers’ was positively associated with alcohol abuse, whereas ‘using the internet to contact peers’ and ‘using the internet primarily to access social networking sites’ were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology. [ABSTRACT FROM PUBLISHER]

Diurnal preference is an individual's preference for daily activities and sleep timing and is strongly correlated with the underlying circadian clock and the sleep-wake cycle validating its use as an indirect circadian measure in humans. Recent research has implicated DNA methylation as a mechanism involved in the regulation of the circadian clock system in humans and other mammals. In order to evaluate the extent of epigenetic differences associated with diurnal preference, we examined genome-wide patterns of DNA methylation in DNA from monozygotic (MZ) twin-pairs discordant for diurnal preference. MZ twins were selected from a longitudinal twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. Fifteen pairs of MZ twins were identified in which one member scored considerably higher on the Horne–Ostberg Morningness–Eveningness Questionnaire (MEQ) than the other. Genome-wide DNA methylation patterns were assessed in twins’ buccal cell DNA using the Illumina Infinium HumanMethylation450 BeadChips. Quality control and data pre-processing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. Our data indicate that DNA methylation differences are detectable in MZ twins discordant for diurnal preference. Moreover, downstream gene ontology (GO) enrichment analysis on the top-ranked diurnal preference associated DMPs revealed significant enrichment of pathways that have been previously associated with circadian rhythm regulation, including cell adhesion processes and calcium ion binding. [ABSTRACT FROM PUBLISHER]

Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10−8), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects. [ABSTRACT FROM PUBLISHER]

Aggressive behavior is highly heritable, while environmental influences, particularly early in life, are also important. Epigenetic mechanisms, such as DNA methylation, regulate gene expression throughout development and adulthood, and may mediate genetic and environmental effects on complex traits. We performed an epigenome-wide association study (EWAS) to identify regions in the genome where DNA methylation level is associated with aggressive behavior. Subjects took part in longitudinal survey studies from the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2004 and 2011 (N = 2,029, mean age at blood sampling = 36.4 years, SD = 12.4, females = 69.2%). Aggressive behavior was rated with the ASEBA Adult Self-Report (ASR). DNA methylation was measured in whole blood by the Illumina HM450k array. The association between aggressive behavior and DNA methylation level at 411,169 autosomal sites was tested. Association analyses in the entire cohort showed top sites at cg01792876 (chr8; 116,684,801, nearest gene = TRPS1, p = 7.6 × 10−7, False discovery rate (FDR) = 0.18) and cg06092953 (chr18; 77,905,699, nearest gene = PARD6G-AS1, p = 9.0 ×10−7, FDR = 0.18). Next, we compared methylation levels in 20 pairs of monozygotic (MZ) twins highly discordant for aggression. Here the top sites were cg21557159 (chr 11; 107,795,699, nearest gene = RAB39, p = 5.7 × 10−6, FDR = 0.99), cg08648367 (chr 19; 51,925,472, nearest gene = SIGLEC10, p = 7.6 × 10−6, FDR = 0.99), and cg14212412 (chr 6; 105,918,992, nearest gene = PREP, p = 8.0 × 10−6, FDR = 0.99). The two top hits based on the entire cohort showed the same direction of effect in discordant MZ pairs (cg01792876, Pdiscordant twins = 0.09 and cg06092953, Pdiscordant twins = 0.24). The other way around, two of the three most significant sites in discordant MZ pairs showed the same direction of effect in the entire cohort (cg08648367, Pentire EWAS = 0.59 and cg14212412, Pentire EWAS = 3.1 × 10−3). Gene ontology analysis highlighted significant enrichment of various central nervous system categories among higher-ranking methylation sites. Higher-ranking methylation sites also showed enrichment for DNase I hypersensitive sites and promoter regions, showing that DNA methylation in peripheral tissues is likely to be associated with aggressive behavior. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to address two methodological issues that have called into question whether previously reported gene–environment interaction (GxE) effects for adolescent alcohol use are ‘real’. These issues are (1) the potential correlation between the environmental moderator and the outcome across twins and (2) non-linear transformations of the behavioral outcome. Three environments that have been previously studied (peer deviance, parental knowledge, and potentially stressful life events) were examined here. For each moderator (peer deviance, parental knowledge, and potentially stressful life events), a series of models was fit to both a raw and transformed measure of monthly adolescent alcohol use in a sample that included 825 dizygotic (DZ) and 803 monozygotic (MZ) twin pairs. The results showed that the moderating effect of peer deviance was robust to transformation, and that although the significance of moderating effects of parental knowledge and potentially stressful life events were dependent on the scale of the adolescent alcohol use outcome, the overall results were consistent across transformation. In addition, the findings did not vary across statistical models. The consistency of the peer deviance results and the shift of the parental knowledge and potentially stressful life events results between trending and significant, shed some light on why previous findings for certain moderators have been inconsistent and emphasize the importance of considering both methodological issues and previous findings when conducting and interpreting GxE analyses. [ABSTRACT FROM PUBLISHER]

Pregnancy- and birth-related factors may have an effect on handedness. Compared with singletons, twins have a lower birth weight, shorter gestational age, and are at higher risk for birth complications. We tested whether the prevalence of left-handedness is higher among twins than singletons, and if so, whether that difference is fully explained by pregnancy and birth-related differences between twins and singletons. We analyzed Finnish population-based datasets; included were 8,786 twins and 5,892 singletons with information on birth weight (n = 12,381), Apgar scores (n = 11,129), and gestational age (n = 11,811). Two twin cohorts were involved: FinnTwin12 included twins born during 1983–1987, and FinnTwin16 included twins born during 1974–1979. We had two comparison groups of singletons: 4,101 individuals born during 1986–1988 and enrolled in the Helsinki Ultrasound Trial, and 1,791 individuals who were partners of FinnTwin16 twins. We used logistic regression models with writing hand as the outcome for comparison and evaluating effects of covariates. Left-handedness was more common in twins (9.67%) than in singletons (8.27%; p = .004). However, Apgar scores were associated with handedness, and after controlling for covariates, we found no difference in the prevalence of left-handedness between twins and singletons. Increased left-handedness among twins, often reported by others, was evident in our data, but only among our older twin cohorts, and that association disappeared after removing effects of perinatal covariates. [ABSTRACT FROM PUBLISHER]

Background: Few studies examining the genetic architecture of cigarette smoking have focused on adolescents or examined developmental changes in additive genetic, shared environment, and unique environmental influences on liability to initiate cigarette smoking and quantity of cigarettes smoked. The aim of this study was to add to the literature on liability to initiate and use cigarettes during adolescence using a nationally representative sample.Method: Data for this study came from adolescent and young adult twin pairs (aged 14-33 years) from the National Longitudinal Study of Adolescent to Adult Health. We ran a series of developmental causal-contingent-common pathway models to examine whether additive genetic, shared, and unique environmental influences on liability to the initiation of cigarette use are shared with those on smoking quantity, and whether their contributions change across development.Results: We found evidence for a developmental shift in genetic and shared environmental contributions to cigarette use. Early in adolescence, genetic and environmental influences work independently on liability to cigarette smoking initiation and quantity of cigarettes smoked, but liability to these behaviors becomes correlated as individuals age into young adulthood.Conclusions: These findings provide insight into the causal processes underlying the liability to smoke cigarettes. With age, there is greater overlap in the genetic and environmental factors that influence the initiation of cigarette smoking and quantity of cigarettes smoked. [ABSTRACT FROM AUTHOR]

We analyzed the association between mean height and old age cognition in two Nordic twin cohorts with different childhood living conditions. The cognitive performance of 4720 twin individuals from Denmark (mean age 81.6 years, SD = 4.59) and Finland (mean age 74.4 years, SD = 5.26) was measured using validated cognitive screens. Taller height was associated with better cognitive performance in Finland (β-estimates 0.18 SD/10cm, p value < .001, for men and 0.13 SD, p = .008, for women), but this association was not significant in Denmark (β-estimates 0.0093 SD, p value = .16, for men and 0.0075 SD, p value = .016, for women) when adjusted for age and education/social class. Among Finnish participants higher variability of cognitive performance within shorter height quintiles was observed. Analysis using gene-environment interaction models showed that environmental factors exerted a greater impact on cognitive performance in shorter participants, whereas in taller participants' it was explained mainly by genetic factors. Our results suggest that shorter participants with childhood adversity are more vulnerable to environmental risk factors for cognitive impairment. [ABSTRACT FROM PUBLISHER]

A twin item factor analytic model was developed to test for the presence of noninvariant age, sex, and age by sex interaction effects on the individual DSM-III-R criteria for major depression (MD). Based on 1-year reports, six of the nine MD criteria and duration requirement were found to have covariate factor loading and/or threshold effects that significantly deviated from their corresponding factor level expectations. A significant age effect was found for the binary duration variable factor loading. The ‘loss of interest’, ‘weight problems’ and ‘psychomotor problems’ criteria all displayed forms of threshold only effects. ‘Depressed mood’, ‘fatigue’, and ‘feeling worthless’ had more complex patterns that included both factor loading and threshold effects. A significant factor age by sex interaction effect indicating an increasing female mean difference with age was found to be largely associated with the presence of differential threshold covariate effects. Disagreement between estimated factor scores and DSM-derived affected vs. unaffected classification was ∼ 1.3%. Status on the duration requirement was found to be the one feature common to all discrepancies. The MD criteria set provided maximum information for calibrating MD factor scores in the scale region where discrepancies occurred. The dimensional modeling results are discussed in the broader context of epidemiological research and clinical assessment of major depression. [ABSTRACT FROM PUBLISHER]

To determine the relationship between the genetic and environmental risk factors for externalizing psychopathology and mental wellbeing, we examined detailed measures of emotional, social and psychological wellbeing, and a history of alcohol-related problems and smoking behavior in the last year in 1,386 individual twins from same-sex pairs from the MIDUS national US sample assessed in 1995. Cholesky decomposition analyses were performed withthe Mx program. The best fit model contained one highly heritable common externalizing psychopathology factor for both substance use/abuse measures, and one strongly heritable common factor for the three wellbeing measures. Genetic and environmental risk factors for externalizing psychopathology were both negatively associated with levels of mental wellbeing and accounted for, respectively, 7% and 21% of its genetic and environmental influences. Adding internalizing psychopathology assessed in the last year to the model, genetic risk factors unique for externalizing psychopathology were now positively related to levels of mental wellbeing, although accounting for only 5% of the genetic variance. Environmental risk factors unique to externalizing psychopathology continued to be negatively associated with mental wellbeing, accounting for 26% of the environmental variance. When both internalizing psychopathology and externalizing psychopathology are associated with mental wellbeing, the strongest risk factors for low mental wellbeing are genetic factors that impact on both internalizing psychopathology and externalizing psychopathology, and environmental factors unique to externalizing psychopathology. In this model, genetic risk factors for externalizing psychopathology predict, albeit weakly, higher levels of mental wellbeing. [ABSTRACT FROM AUTHOR]

The current article examines the assumptions of the MZ co-twin control method that has been applied in attempts to gain more accurate estimates of the returns to education by naturally ‘controlling’ for individual differences on which MZ twins are matched. The current study examined 1738 MZ and 926 DZ twins from Minnesota, including 133 pairs of MZ and 101 pairs of DZ twins discordant for university attendance. They were assessed prospectively on personality, intelligence, GPA, and academic motivation; a subset also has reported income at age 29. MZ twins discordant for university attendance differed significantly and prospectively on verbal IQ, personality traits, and GPA. While MZ co-twin control studies can provide more accurate estimates of the returns to education than analyses of single individuals, these studies do not entirely obviate the need to control for differences between university students and non-students that predate university attendance and might account for income differentials and even non-monetary outcomes. [ABSTRACT FROM PUBLISHER]

In order to estimate the influence of genetic and environmental factors on 'crying without a cause' and 'being easily upset' in 2-year-old children, a large twin study was carried out. Prospective data were available for ~18,000 2-year-old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis was performed using structural equation modeling in the Mx software package. The influence of maternal personality characteristics and demographic and lifestyle factors was tested to identify specific risk factors that may underlie the shared environment of twins. Furthermore, it was tested whether crying without a cause and being easily upset were predictive of later internalizing, externalizing and attention problems. Crying without a cause yielded a heritability estimate of 60% in boys and girls. For easily upset, the heritability was estimated at 43% in boys and 31% in girls. The variance explained by shared environment varied between 35% and 63%. The correlation between crying without a cause and easily upset (r = .36) was explained both by genetic and shared environmental factors. Birth cohort, gestational age, socioeconomic status, parental age, parental smoking behavior and alcohol use during pregnancy did not explain the shared environmental component. Neuroticism of the mother explained a small proportion of the additive genetic, but not of the shared environmental effects for easily upset. Crying without a cause and being easily upset at age 2 were predictive of internalizing, externalizing and attention problems at age 7, with effect sizes of .28-.42. A large influence of shared environmental factors on crying without a cause and easily upset was detected. Although these effects could be specific to these items, we could not explain them by personality characteristics of the mother or by demographic and lifestyle factors, and we recognize that these effects may reflect other maternal characteristics. A substantial influence of genetic factors was found for the two items, which are predictive of later behavioral problems. [ABSTRACT FROM AUTHOR]

Mental health is increasingly defined not only by the absence of illness but by the presence of subjective well-being (SWB). Previous cohort studies have consistently shown that indicators of SWB predict favorable life outcomes, including better mental and somatic health, and longevity. The favorable effects associated with SWB have prompted new research aimed at raising happiness and wellbeing through individual interventions and public health initiatives. Standard observational studies of individual-level associations, however, are subject to potential confounding of exposure and outcome by shared genes and environment. The present study explored the association between SWB and increased longevity, using twin pair analyses to determine whether the association is consistent with causality or is due to genetic or environmental confounding. The study sample of 3,966 twins aged 70 or older, followed for a median time period of 9 years, was drawn from the population-based Longitudinal Study of Aging Danish Twins (LSADT). The association between SWB, operationalized as affect and life satisfaction, and all-cause mortality risk was examined using between-individual and within-pair survival analyses. As expected, at the individual level, SWB predicted increased longevity. Exposure effects were also present in unadjusted and adjusted within-pair analyses of 400 dizygotic (DZ) pairs and 274 monozygotic (MZ) pairs, indicating that SWB is associated with increased longevity independent of familial factors of genes and shared environment. [ABSTRACT FROM AUTHOR]

A set of 10 SNPs associated with reading ability in 7-year-olds was reported based on initial pooled analyses of 100K SNP chip data, with follow-up testing stages using pooling and individual testing. Here we examine this association in an adolescent population sample of Australian twins and siblings (N = 1177) aged 12 to 25 years. One (rs1842129) of the 10 SNPs approached significance (P = .05) but no support was found for the remaining 9 SNPs or the SNP set itself. Results indicate that these SNPs are not associated with reading ability in an Australian population. The results are interpreted as supporting use of much larger SNP sets in common disorders where effects are small. [ABSTRACT FROM AUTHOR]

Twin studies suggest that global and regional brain volumes are highly heritable. However, estimates of heritability vary across development. Given that all twin studies are open to the potential criticism of non-generalizability due to differences in intrauterine environment between twins and singletons, these age effects may reflect the influence of perinatal environmental factors, which are unique to twins and which may be especially evident early in life. To address this question, we compared brain volumes and the relationship of brain volumes to gestational age in 136 singletons (67 male, 69 female) and 154 twins (75 male, 79 female; 82 DZ, 72 MZ) who had received high resolution MRI scans of the brain in the first month of life. Intracranial volume, total white matter, and ventricle volumes did not differ between twins and singletons. However, cerebrospinal fluid and frontal white matter volume was greater in twins compared to singletons. While gray matter volumes at MRI did not differ between groups, the slope of the relationship between total and cortical gray matter and gestational age at the MRI scan was steeper in MZ twins compared to DZ twins. Post-hoc analyses suggested that gray matter development is delayed in MZ twins in utero and that they experience 'catch-up' growth in the first month of life. These differences should be taken into account when interpreting and designing studies in the early postnatal period. [ABSTRACT FROM AUTHOR]

Postcoital psychological symptoms (PPS) is a virtually unexplored phenomenon in the female population even though women frequently complain about irritability and motiveless crying after intercourse and/or orgasm. The aim of this study was to explore the epidemiology and genetic influences of PPS in a UK population sample of women. 1,489 unselected female twins aged 18-85 completed questions on recent and persistent PPS and potential risk factors. Standard methods of quantitative genetic analysis were used to model latent genetic and environmental factors influencing variation in PPS. For identification of potential risk factors, regression analyses were conducted. Phenotypic variation in PPS was explored using a genetic variance component analysis (VCA) approach. We found 3.7% of women reported suffering from recent PPS and 7.7% from persistent PPS. Relationship satisfaction and experience of abuse were found to be independently associated with recent (OR 4.5, 95% CI 4.13-4.87 and OR 1.3, 95% CI 1.02-1.34, respectively) and persistent PPS (OR 2.53, 95% CI 2.17-2.81 and OR 1.16, 95% CI 1.09-1.26, respectively). VCA revealed that phenotypic variance was best explained by an additive genetic (AE) model, ascribing 28% (for recent PPS) and 26% (for persistent PPS) of phenotypic variance to additive genetic effects, with the rest being a result of individual experiences and random measurement error. To our knowledge, this is the first and largest study investigating the epidemiology of PPS. It seems that the most important targets for intervention and prevention occur outside of the family, such as relationship quality and satisfaction, and history of abuse. [ABSTRACT FROM AUTHOR]

Molecular genetic research has provided some evidence for the association between depression and metabolic disorders. We sought to determine if molecular findings are reflected in twin analyses testing if common genetic and environmental risk factors contribute to the co-occurrence of diabetes and depression. Data to derive depression and diabetes were collected from 1,237 male-male twins who participated in the 2005 Vietnam Era Twin Study of Aging (VETSA). The 1,237 twins were comprised of 347 MZ pairs, 3 MZ singletons, 267 DZ pairs and 6 unpaired twins. Depression was defined as a score below 46 on the Short Form-36 mental component summary score. Diabetes was defined by self report, use of anti-diabetic medications and insulin. Twin models were fit to estimate the correlation of genetic and environmental contributions to depression and diabetes. Consistent with other studies these data support the association between depression and diabetes (OR = 1.7; 95%CI: 1.1-2.7). Genetic vulnerability accounted for 50% (95%CI: 32%-65%) of the variance in risk for depression and 69% (95%CI: 52%-81%) of the variance in risk for diabetes. The genetic correlation between depression and diabetes was r = 0.19 (95%CI: 0-0.46) and the non-shared environmental correlation was r = 0.09 (95% CI: 0-0.45). Overall there is little evidence that common genetic and environmental factors account for the co-occurrence of depression and diabetes in middle aged men. Further research in female twins and larger cohorts is warranted. [ABSTRACT FROM AUTHOR]

Cytotoxic precipitation of free α-globin monomers and its production of reactive oxygen species cause red cell membrane damage that leads to anemia and eventually ineffective erythropoiesis in β-thalassemia. Alpha hemoglobin stabilizing protein (AHSP) was found to bind only to free α-globin monomers creating a stable and inert complex which remains soluble in the cytoplasm thus preventing harmful precipitations. Alpha hemoglobin stabilizing protein was shown to bind nascent α-globin monomers with transient strength before transferring α-globin to β-globin to form hemoglobin tetramer. A classical twin study would be beneficial to investigate the role of genetics and environment in the variation of alpha hemoglobin stabilizing protein expression as this knowledge will enable us to determine further investigations with regards to therapeutic interventions if alpha hemoglobin stabilizing protein is to be a therapeutic agent for β-thalassemia. This study investigates the heritability influence of alpha hemoglobin stabilizing protein expression and factors that may contribute to this. Results indicated that a major proportion of alpha hemoglobin stabilizing protein expression was influenced by genetic heritability (46%) with cis-acting factors accounting for 19% and trans-acting factors at 27%. [ABSTRACT FROM AUTHOR]

Using longitudinal cross-lagged analysis to infer causal directions of reciprocal effects is one of the most important tools in the developmental armamentarium. The strength of these analyses can be enhanced by analyzing the genetic and environmental aetiology underlying cross-lagged relationships, for which we present a novel approach here. Our approach is based on standard Cholesky decomposition. Standardized path coefficients are employed to assess genetic and environmental contributions to cross-lagged associations. We indicate how our model differs importantly from another approach that does not in fact analyze genetic and environmental contributions to cross-lagged associations. As an illustration, we apply our approach to the analysis of the cross-lagged relationships between self-perceived abilities and school achievement from age 9 to age 12. Self-perceived abilities of 3852 pairs of twins from the UK Twins Early Development Study were assessed using a self-report scale. School achievement was assessed by teachers based on UK National Curriculum criteria. The key cross-lagged association between self-perceived abilities at age 9 and school achievement at age 12 was mediated by genetic influences (28%) as well as shared (55%) and non-shared (16%) environment. The reverse cross-lagged association from school achievement at 9 to self-perceived abilities at 12 was primarily genetically mediated (73%). Unlike the approach to cross-lagged genetic analysis used in recent research, our approach assesses genetic and environmental contributions to cross-lagged associations per se. We discuss implications of finding that genetic factors contribute to the cross-lag between self-perceived abilities at age 9 and school achievement at age 12. [ABSTRACT FROM AUTHOR]

Opioids are the cornerstone medication for the treatment of moderate to severe pain. However, analgesic opioid requirements and the propensity to suffer from aversive opioid effects, including fatal respiratory depression and addiction, vary widely among patients. The factors underlying the substantial response variance remain largely unknown and need clarification for using opioids more effectively in appropriately selected patients. This ongoing study takes advantage of the twin paradigm to estimate the genetic and environmental contributions to inter-individual differences in opioid responses. Evidence of significant heritability will justify more detailed and extensive genomic studies. The enrollment target is 80 monozygotic and 45 dizygotic twin pairs who undergo a target-controlled infusion of the opioid alfentanil and saline placebo in sequential but randomized order. In a laboratory-type setting, well-defined pharmacodynamic endpoints are measured to quantify pain sensitivity, analgesic opioid effects, and aversive opioid effects including respiratory depression, sedation and reinforcing affective responses. First results obtained in 159 participants provide evidence for the feasibility and utility of this interventional study paradigm to estimate familial aggregation and heritability components of relevant drug effects. Areas highlighted in this report include recruitment strategies, required infrastructure and personnel, selection of relevant outcome measures, drug infusion algorithm minimizing pharmacokinetic variability, and considerations for optimizing data quality and quantity without hampering feasibility. Applying the twin paradigm to complex and potentially harmful studies comprehensively characterizing pharmacological response profiles is without much precedent. Methods and first results including heritability estimates for heat and cold pain sensitivity should be of interest to investigators considering similar studies. [ABSTRACT FROM AUTHOR]

Self-rated health questions have been proven to be a highly reliable and valid measure of overall health as measured by other indicators in many population groups. It also has been shown to be a very good predictor of mortality, chronic or severe diseases, and the need for services, and is positively correlated with clinical assessments. Genetic factors have been estimated to account for 25-64% of the variance in the liability of self-rated health. The aim of the present study was to identify Single Nucleotide Polymorphisms (SNPs) underlying the heritability of self-rated health by conducting a genome-wide association analysis in a large sample of 6,706 Australian individuals aged 18-92. No genome wide significant SNPs associated with self-rated health could be identified, indicating that self-rated health may be influenced by a large number of SNPs with very small effect size. A very large sample will be needed to identify these SNPs. [ABSTRACT FROM AUTHOR]

Abstract This study employs multiple regression models based on DeFries and Fulker (1985), and a large sample of twins, to assess heritability in attitudes towards economic risk, and the extent to which this heritability differs between males and females. Consistent with Cesarini et al. (2009), it is found that attitudes towards risk are moderately heritable, with about 20 percent of the variation in these attitudes across individuals being linked to genetic differences. This value is less than one-half the estimates reported by Zyphur et al. (2009) and Zhong et al. (2009). While females are more risk averse than males, there is no evidence that heritability in attitudes towards risk differs between males and females. Even though heritability is shown to be important to economic risk-taking, the analyses suggest that multivariate studies of the determinants of attitudes towards risk which to not take heritability into consideration still provide reliable estimates of the partial effects of other key variables, such as gender and educational attainment. [ABSTRACT FROM AUTHOR]

Childhood sexual abuse (CSA) and physical abuse (CPA) are well-established risk-factors for a wide of range of proximal and distal outcomes. The lack of availability of an optimal design for examining abuse and its consequences has resulted in the use of various approaches, each having its own limitations. We describe the Childhood Trauma Study, which ascertained families from a large young adult Australian twin cohort on the basis of twins' responses to screening questions assessing CSA and CPA. We report data from 3407 participants including twins, non-twin siblings, and their parents. Our data demonstrate the feasibility of using a comprehensive assessment to evaluate retrospective history of childhood abuse in an adult sample. We observed that risk for each form of abuse increased incrementally with the number of parents with alcohol problems. Psychometric properties of our measures of CSA and CPA including reasonable long-term stability, construct validity, and evidence of familial corroboration compare favorably with those of other reports in which samples were considerably younger and assessments were repeated over shorter intervals. [ABSTRACT FROM AUTHOR]

Human height and body mass index are influenced by a large number of genes, each with small effects, along with environment. To identify common genetic variants associated with these traits, we performed genome-wide association studies in 11,536 individuals composed of Australian twins, family members, and unrelated individuals at approximately 550,000 genotyped SNPs. We identified a single genome-wide significant variant for height (P value=1.06x10(-9)) located in HHIP, a well-replicated height-associated gene. Suggestive levels of association were found for other known genes associated with height (P values<1x10(-6)): ADAMTSL3, EFEMP1, GPR126, and HMGA2; and BMI (P values<1x10(-4)): FTO and MC4R. Together, these variants explain less than 2% of total phenotypic variation for height and 0.5% for BMI. [ABSTRACT FROM AUTHOR]

Gemini is a cohort study of young twins in the United Kingdom designed to assess genetic and environmental influences on early childhood weight trajectories with a focus on infant appetite and the family environment. A total of 2402 families with twins born in England and Wales between March and December 2007 agreed to participate and returned completed baseline questionnaires. The sample includes 1586 same-sex and 816 opposite-sex twins. The study is currently funded for 5 years of follow-up, but is planned to continue into early adolescence and beyond, pending funding. With current funding of the study, families will be followed up when twins are: 8 months old (baseline), and then at 15, 20, 24, 36 and 48 months of age. Gemini is in its early stages, with baseline and first follow-up data collection completed. This is the first twin cohort to focus on childhood weight gain with detailed and repeated measures of children's appetite, food preferences, activity behavior and parental feeding styles, alongside detailed and repeated collection of anthropometrics. This article reviews the rationale for the Gemini study, its representativeness and the main measures. [ABSTRACT FROM AUTHOR]

Research on twin-singleton differences in externalizing and internalizing problems in childhood is largely cross-sectional and yields contrasting results. The goal of this study was to compare developmental trajectories of externalizing and internalizing problems in 6- to 12-year-old twins and singletons. Child Behavior Checklist (CBCL) maternal reports of externalizing and internalizing problems were obtained for a sample of 9651 twins from the Netherlands Twin Register and for a representative general population sample of 1351 singletons. Latent growth modeling was applied to estimate growth curves for twins and singletons. Twin-singleton differences in the intercepts and slopes of the growth curves were examined. The developmental trajectories of externalizing problems showed a linear decrease over time, and were not significantly different for twins and singletons. Internalizing problems seem to develop similarly for twins and singletons up to age 9. After this age twins' internalizing symptoms start to decrease in comparison to those of singletons, resulting in less internalizing problems than singletons by the age of 12 years. Our findings confirm the generalizability of twin studies to singleton populations with regard to externalizing problems in middle and late childhood. The generalizability of studies on internalizing problems in early adolescence in twin samples should be addressed with care. Twinship may be a protective factor in the development of internalizing problems during early adolescence. [ABSTRACT FROM AUTHOR]

A recent study has suggested that aggressive (AGG) and non-aggressive, rule-breaking (RB) antisocial behavior evidence differential and subtype-specific patterns of genetic expression during development. Namely, although genetic influences on RB increase dramatically during early- to mid-adolescence, genetic influences on AGG appear to remain stable. As no other study has examined age-related change in AGG versus RB, more research is clearly needed before any firm conclusions can be drawn. The current study thus examined whether and how age impacted genetic and environmental influences on AGG and RB in a sample of 252 10- to 15-year-old twin pairs assessed as part of the Michigan State University Twin Registry (MSUTR). Results constructively replicated and extended prior findings, indicating that while the magnitude of genetic and environmental influences on AGG remained stable across adolescence, genetic influences on RB increased dramatically with age. Such findings provide additional support for etiological distinctions within the broader construct of antisocial behavior based on the presence or absence of aggression, and offer insights into the expression of genetic influences during development. [ABSTRACT FROM AUTHOR]

Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established. We examined 4-hour test–retest reliability and 10 month test–retest stability of individual differences in gene expression in ten 12-year-old children. Blood was collected on four occasions: 10 a.m. and 2 p.m. on Day 1 and 10 months later at 10 a.m. and 2 p.m. Total RNA was hybridized to Affymetrix-U133 plus 2.0 arrays. For each probeset, the correlation across individuals between 10 a.m. and 2 p.m. on Day 1 estimates test–retest reliability. We identified 3,414 variable and abundantly expressed probesets whose 4-hour test–retest reliability exceeded .70, a conventionally accepted level of reliability, which we had 80% power to detect. Of the 3,414 reliable probesets, 1,752 were also significantly reliable 10 months later. We assessed the long-term stability of individual differences in gene expression by correlating the average expression level for each probe-set across the two 4-hour assessments on Day 1 with the average level of each probe-set across the two 4-hour assessments 10 months later. 1,291 (73.7%) of the 1,752 probe-sets that reliably detected individual differences across 4 hours on two occasions, 10 months apart, also stably detected individual differences across 10 months. Heritability, as estimated from the MZ twin intraclass correlations, is twice as high for the 1,752 reliable probesets versus all present probesets on the array (0.68 vs 0.34), and is even higher (0.76) for the 1,291 reliable probesets that are also stable across 10 months. The 1,291 probesets that reliably detect individual differences from a single peripheral blood collection and stably detect individual differences over 10 months are promising targets for research on the causes (e.g., eQTLs) and correlates (e.g., psychopathology) of individual differences in gene expression. [ABSTRACT FROM AUTHOR]

The analysis of genetic and environmental contributions to preterm birth is not straightforward in family studies, as etiology could involve both maternal and fetal genes. Markov Chain Monte Carlo (MCMC) methods are presented as a flexible approach for defining user-specified covariance structures to handle multiple random effects and hierarchical dependencies inherent in children of twin (COT) studies of pregnancy outcomes. The proposed method is easily modified to allow for the study of gestational age as a continuous trait and as a binary outcome reflecting the presence or absence of preterm birth. Estimation of fetal and maternal genetic factors and the effect of the environment are demonstrated using MCMC methods implemented in WinBUGS and maximum likelihood methods in a Virginia COT sample comprising 7,061 births. In summary, although the contribution of maternal and fetal genetic factors was supported using both outcomes, additional births and/or extended relationships are required to precisely estimate both genetic effects simultaneously. We anticipate the flexibility of MCMC methods to handle increasingly complex models to be of particular relevance for the study of birth outcomes. [ABSTRACT FROM AUTHOR]

Objective: As post-pregnancy weight retention in women is a risk factor for obesity later in life, we assessed the changes in magnitude of genetic and environmental variation in BMI due to parity in an Australian female sample, comprising 11,915 female twins and their sisters. Results: Total variance of BMI increased with parity, primarily driven by an increase in nonadditive genetic variance. This finding was of particular interest given Gutersohn et al's (2000) report of recessive association between post-partum weight retention and the 825T allele of the GNβ3 gene (rs5443) at 12p13.31. Hence, we attempted to replicate this association and test an additional three SNPs also located near or on GNβ3 (rs10744716 (upstream), rs5442 (exon 10), rs5446 (exon 11)) in a sample of 3131 females and 1693 males from 2585 twin families. No association was found between these SNPs among females, even when allowing for a genotype by parity effect. However, a significant association was observed among males for rs10744716 (χ22 = 10.22, p = 0.006; effect size = 0.47kg/m2), representing a novel association between a region upstream of GNβ3 and male BMI. [ABSTRACT FROM AUTHOR]

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

All 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. [ABSTRACT FROM AUTHOR]

Objective: A recent Children-of-Female-Twin design suggests that the association between maternal alcohol use disorder and offspring ADHD is due to a combination of genetic and environmental factors, such as prenatal nicotine exposure. We present here a complementary analysis using a Children-of-Male-Twin design examining the association between paternal alcoholism and offspring attention deficit hyperactivity problems (ADHP).Methods: Children-of-twins design: offspring were classified into 4 groups of varying genetic and environmental risk based on father and co-twin's alcohol dependence status.Results: Univariate results are suggestive of a genetic association between paternal alcohol dependence and broadly defined offspring ADHP. Specifically, offspring of male twins with a history of DSM-III-R alcohol dependence, as well as offspring of non-alcohol dependent monozygotic twins whose co-twin was alcohol dependent, were significantly more likely to exhibit ADHP than control offspring. However, multivariate models show maternal variables independently predicting increased risk for offspring ADHP and significantly decreased support for a genetic mechanism of parent-to-child transmission.Conclusions: In support of earlier work, maternal variables (i.e., maternal ADHD and prenatal exposure) were strongly associated with child ADHP; however, the role of paternal alcohol dependence influences was not definitive. While genetic transmission may be important, the association between paternal alcohol dependence and child ADHP is more likely to be indirect and a result of several pathways. [ABSTRACT FROM AUTHOR]

This study presents a general model of two binary variables and applies it to twin sex pairing data from 21 twin data sources to estimate the frequency of dizygotic twins. The purpose of this study is to clarify the relationship between maximum likelihood and Weinberg's differential rule zygosity estimation methods. We explore the accuracy of these zygosity estimation measures in relation to twin ascertainment methods and the probability of a male. Twin sex pairing data from 21 twin data sources representing 15 countries was collected for use in this study. Maximum likelihood estimation of the probability of dizygotic twins is applied to describe the variation in the frequency of dizygotic twin births. The differences between maximum likelihood and Weinberg's differential rule zygosity estimation methods are presented as a function of twin data ascertainment method and the probability of a male. Maximum likelihood estimation of the probability of dizygotic twins ranges from 0.083 (95% approximate CI: 0.082, 0.085) to 0.750 (95% approximate CI: 0.749, 0.752) for voluntary ascertainment data sources and from 0.374 (95% approximate CI: 0.373, 0.375) to 0.987 (95% approximate CI: 0.959, 1.016) for active ascertainment data sources. In 17 of the 21 twin data sources differences of 0.01 or less occur between maximum likelihood and Weinberg zygosity estimation methods. The Weinberg and maximum likelihood estimates are negligibly different in most applications. Using the above general maximum likelihood estimate, the probability of a dizygotic twin is subject to substantial variation that is largely a function of twin data ascertainment method. [ABSTRACT FROM AUTHOR]

The extended twin kinship design allows the simultaneous testing of additive and nonadditive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission (Eaves et al., 1999). It also handles the contribution of these sources of variance to the (co)variation of multiple phenotypes. Keller et al. (2008) extended this comprehensive model for family resemblance to allow or a flexible specification of assortment and vertical transmission. As such, it provides a general framework which can easily be reduced to fit subsets of data such as twin-parent data, children-of-twins data, etc. A flexible Mx specification of this model that allows handling of these various designs is presented in detail and applied to data from the Virginia 30,000. Data on height, body mass index, smoking status, church attendance, and political affiliation were obtained from twins and their families. Results indicate that biases in the estimation of variance components depend both on the types of relative available for analysis, and on the underlying genetic and environmental architecture of the phenotype of interest. [ABSTRACT FROM AUTHOR]

This study examines the probability of twins by birth year, maternal race-ethnicity, age, and parity and the influences of these demographic factors on the probability of male in twins and singletons in a large, racially diverse population. Recent publications note steep increases in twin births while the probability of male births has been reported to vary by parental race-ethnicity and age and birth order. Probability of male stratified by plurality has not been investigated in California prior to this study. Cubic spline estimates and Poisson regression techniques were employed to describe trends in twins and males using California vital statistics birth and fetal death records over the period from 1983-2003. This study includes 127,787 twin pair and 11,025,106 singleton births. The probability of twins varied by birth year, maternal race-ethnicity, age, and parity. The probability of twins increased by 10.1% from 1983-1992 and increased by 20.1% from 1993-2003, nearly doubling the previous increase. All maternal race-ethnicity groups showed increases in probability of twins with increasing maternal age. Parous women compared to nulliparous women had larger increases in the probability of twins. The probability of males in twins decreased from 1983-1992 and increased from 1993-2003; while in singletons the probability appeared unchanged. These findings show increases in the probability of twins in California from 1983-2003 and identify maternal age, race-ethnicity, and parity groups most likely to conceive twins. The cause of the increase in twins is unknown but coincides with trends towards delayed childbearing and increased use of subfertility treatments. [ABSTRACT FROM AUTHOR]

Two major challenges to conducting a community-based twin study of pathological gambling (PG) disorder are that: (a) it is relatively rare, and (b) individuals with the disorder in the community may be difficult to locate and recruit. We describe a new study of 4,764 individuals recruited from the Australian Twin Registry in which we attempt to effectively deal with the first challenge and examine the impact of the second challenge. The lifetime prevalence of DSM-IV PG in this Australian twin sample was 2.2%, which is 400-500% higher than has been obtained in prevalence surveys conducted in the United States. A number of predictors of non-participation were identified, including a lifetime PG disorder diagnosis, but these did not have a large net effect on the estimated number of individuals with PG or related characteristics in the twin sample. Results of biometric modeling suggested that the effect of genetic, shared family environmental, and nonshared environmental influences on the propensity to engage in 11 different specific forms of gambling (e.g., playing the lottery, betting on horse or dog races, playing electronic gaming machines) were generally moderate, low, and moderate, respectively, with mean parameter estimates obtained of 43%, 10%, and 46%. An intriguing comparison with results from a 1963 US adolescent twin study conducted by Loehlin and Nichols (1976) suggests that: (a) propensity genes for gambling involvement may be more likely to be expressed in the heavy-gambling Australian culture, or that (b) the family environment has a transient effect on the gambling behavior of young people. [ABSTRACT FROM AUTHOR]

The genetic basis of cardiovascular disease (CVD) is complex and still largely elusive. Plasma lipid concentrations are well-established risk factors for cardiovascular disease (CVD), and have adult heritabilities ranging from 0.48 to 0.87. Estimates for adolescents are slightly higher (range 0.71 to 0.82). To identify loci affecting lipid concentrations across adolescence, we analyzed longitudinal lipid data in a sample of 134 monozygotic and 626 dizygotic twin pairs at ages twelve, fourteen and sixteen, and their siblings, from 760 Australian families. Univariate linkage analysis for each phenotype and time point was supplemented by multivariate analysis across the time points. A genome-wide association scan was also performed on a subset of the subjects (N = 441). The strongest linkage was seen for triglycerides on chromosome 6p24.3 (multivariate -log(10) p = 6.81; equivalent LOD = 6.13; p = 1.55 x 10(-7)). Significant linkage was also found for LDL cholesterol on chromosome 2q35 (multivariate -log(10)p = 5.59; equivalent LOD = 4.53; p = 2.57 x 10(-6)). In the association analysis, rs10503840 on 8p21.1 was significantly associated with total cholesterol levels at age fourteen (p = 8.24 x 10(-7), estimated significance threshold 2.45 x 10(-6)). Association at p < 2.25 x 10(-6) was also found between triglycerides at age 12 and rs10507266, in an intron of THRAP2 (MIM 608771) on 12q24.21; and between HDL-C at age 14 and rs10506325 in an intergenic region of 12q13.13. Suggestive evidence of association at ages twelve and fourteen was found between HDL-C and rs10492859 on 16q23 (p = 2.42 x 10(-5) and 2.77 x 10(-4), respectively). Further longitudinal genetic studies of cardiovascular risk factors, focused on critical periods of development or change, are needed. [ABSTRACT FROM AUTHOR]

Recent clinic-based and population-based studies have shown evidence of association between ADHD and autistic symptoms in children and adolescents as well as evidence for genetic overlap between these disorders. The objective of the current study was to confirm the association between autistic and ADHD symptoms in a young adult twin sample assessed by self-report, and investigate whether shared genetic and/or environmental factors can explain the association. We performed twin-based structural equation modeling using self-report data from 11 Social Responsiveness Scale (SRS) items and 12 DSM-IV ADHD inattentive and impulsive symptom items obtained from 674 young adult Australian twins. Phenotypic correlation between autistic and ADHD symptoms was moderate. The most parsimonious univariate models for SRS and ADHD included additive genetic effects and unique environmental effects, without sex differences. ADHD and autistic traits were both moderately heritable. In a bivariate model, genetic correlation (r(g)) between SRS and ADHD was 0.72. Our results suggest that in young adults, a substantial proportion of the genetic influences on self-reported autistic and ADHD symptoms may be shared between the two disorders. [ABSTRACT FROM AUTHOR]

The Thought-Problem scale (TP) of the CBCL assesses symptoms such as hallucinations and strange thoughts/behaviors and has been associated with other behavioral disorders. This study uses parental reports to examine the etiology of variation in TP, about which relatively little is known, in 7-year-old twins. Parental ratings on TP were collected in 8,962 7-year-old twin pairs. Because the distribution of TP scores was highly skewed scores were categorized into 3 classes. The data were analyzed under a threshold liability model with genetic structural equation modeling. Ratings from both parents were simultaneously analyzed to determine the rater agreement phenotype (or common phenotype [TPc]) and the rater specific phenotype [TPs] that represents rater disagreement caused by rater bias, measurement error and/or a unique view of the parents on the child's behavior. Scores on the TP-scale varied as a function of rater (fathers rated fewer problems), sex (boys scored higher) and zygosity (DZ twins scored higher). The TPc explained 67% of the total variance in the parental ratings. Variation in TPc was influenced mainly by the children's genotype (76%). Variance in TPs also showed a contribution of genetic factors (maternal reports: 61%, paternal reports: 65%), indicating that TPs does not only represent rater bias. Shared environmental influences were only found in the TPs. No sex differences in genetic architecture were observed. These results indicate an important contribution of genetic factors to thought problems in children as young as 7 years. [ABSTRACT FROM AUTHOR]