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Blood cell concentrations for most cell types are highly heritable. Data from Nick Martin's twin registry provided much of the data for the early heritability and linkage studies of blood cell related traits and have contributed significantly to more recent genomewide association studies that have successfully identified individual genetic loci. [ABSTRACT FROM AUTHOR]

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcomes. [ABSTRACT FROM AUTHOR]

Quantitative and molecular genetic research requires large samples to provide adequate statistical power, but it is expensive to test large samples in person, especially when the participants are widely distributed geographically. Increasing access to inexpensive and fast Internet connections makes it possible to test large samples efficiently and economically online. Reliability and validity of Internet testing for cognitive ability have not been previously reported; these issues are especially pertinent for testing children. We developed Internet versions of reading, language, mathematics and general cognitive ability tests and investigated their reliability and validity for 10- and 12-year-old children. We tested online more than 2500 pairs of 10-year-old twins and compared their scores to similar internet-based measures administered online to a subsample of the children when they were 12 years old (> 759 pairs). Within 3 months of the online testing at 12 years, we administered standard paper and pencil versions of the reading and mathematics tests in person to 30 children (15 pairs of twins). Scores on Internet-based measures at 10 and 12 years correlated .63 on average across the two years, suggesting substantial stability and high reliability. Correlations of about .80 between Internet measures and in-person testing suggest excellent validity. In addition, the comparison of the internet-based measures to ratings from teachers based on criteria from the UK National Curriculum suggests good concurrent validity for these tests. We conclude that Internet testing can be reliable and valid for collecting cognitive test data on large samples even for children as young as 10 years. [ABSTRACT FROM AUTHOR]

In the late 1980s The Netherlands Twin Register (NTR) was established by recruiting young twins and multiples at birth and by approaching adolescent and young adult twins through city councils. The Adult NTR (ANTR) includes twins, their parents, siblings, spouses and their adult offspring. The number of participants in the ANTR who take part in survey and / or laboratory studies is over 22,000 subjects. A special group of participants consists of sisters who are mothers of twins. In the Young NTR (YNTR), data on more than 50,000 young twins have been collected. Currently we are extending the YNTR by including siblings of twins. Participants in YNTR and ANTR have been phenotyped every 2 to 3 years in longitudinal survey studies, since 1986 and 1991 for the YNTR and ANTR, respectively. The resulting large population-based datasets are used for genetic epidemiological studies and also, for example, to advance phenotyping through the development of new syndrome scales based on existing items from other inventories. New research developments further include brain imaging studies in selected and unselected groups, clinical assessment of psychopathology through interviews, and cross-referencing the NTR database to other national databases. A large biobank enterprise is ongoing in the ANTR in which blood and urine samples are collected for genotyping, expression analysis, and metabolomics studies. In this paper we give an update on the YNTR and ANTR phenotyping and on the ongoing ANTR biobank studies. [ABSTRACT FROM AUTHOR]

The Danish Twin Registry is the oldest national twin register in the world, initiated in 1954, and, by the end of 2005, contained more than 75,000 twin pairs born in the between 1870 and 2004. The Danish Twin Registry is used as a source for studies on the genetic influence on normal variation in clinical parameters associated with the metabolic syndrome and cardiovascular diseases, clinical studies of specific diseases, and aging and age-related health problems. The combination of survey data, clinical data and linkage to national health-related registers enables follow-up studies of both the general twin population and twins from clinical studies. This paper summarizes the newest extension of the register and gives examples of new developments and phenotypes studied. [ABSTRACT FROM AUTHOR]

Background: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors.Methods: We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive 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, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime 'ever' smoking measure was obtained from twins and relatives in the 'Virginia 30,000' sample and the 'Australian 25,000'.Results: Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data.Conclusions: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI. [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]

We identified the genetic variants for eye color by Genome-Wide Association Study (GWAS) in a Dutch Caucasian family-based population sample and examined the genetic correlation between hair and eye color using data from unrelated participants from the Netherlands Twin Register. With the Genome-wide Complex Trait Analysis software package, we found strong genetic correlations between various combinations of hair and eye colors. The strongest positive correlations were found for blue eyes with blond hair (0.87) and brown eyes with dark hair (0.71), whereas blue eyes with dark hair and brown eyes with blond hair showed the strongest negative correlations (-0.64 and -0.94, respectively). Red hair with green/hazel eyes showed the weakest correlation (-0.14). All analyses were corrected for age and sex, and we explored the effects of correcting for principal components (PCs) that represent ancestry and describe the genetic stratification of the Netherlands. When including the first three PCs as covariates, the genetic correlations between the phenotypes disappeared. This is not unexpected since hair and eye colors strongly indicate the ancestry of an individual. This makes it difficult to separate the effects of population stratification and the true genetic effects of variants on these particular phenotypes. [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]

Sex differences in religion are well known, with females generally being more religious than males, and shared environmental factors have been suggested to have a large influence on religiousness. Twins from opposite-sex (OS) and same-sex (SS) pairs may differ because of a dissimilar psycho-social rearing environment and/or because of different exposures to hormones in utero. We hypothesized that OS females may display more masculine patterns of religiousness and, vice versa, that OS males may display more feminine patterns. We used a web-based survey conducted in Denmark, which is a secular society. The survey included 2,997 twins aged 20–40 years, identified through the population-based Danish Twin Registry. We applied la Cour and Hvidt's adaptation of Fishman's three conceptual dimensions of meaning: Cognition, Practice, and Importance, and we used Pargament's measure of religious coping (RCOPE) for the assessment of positive and negative religious coping patterns. Differences between OS and SS twins were investigated using logistic regression for each sex. The analyses were adjusted for dependence within twin pairs. No significant differences in religiousness and religious coping were found for OS and SS twins except that more OS than SS females were members of the Danish National Evangelical Lutheran Church and fewer OS than SS females were Catholic, Muslim, or belonged to other religious denominations. Moreover, OS males at age 12 had higher rates of church attendance than did SS males. This study did not provide evidence for masculinization of female twins with male co-twins with regard to religiousness. Nor did it show any significant differences between OS and SS males except from higher rates of church attendance in childhood among males with female co-twins. [ABSTRACT FROM PUBLISHER]

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]

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]

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]

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]

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]

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]

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]

The finding of a significant gene by environment interaction effect on depression of the serotonin transporter length polymorphism (5-HTTLPR) and the Number of experienced Life Events (NLE) was not replicated in two large meta-analyses (Munafo et al., 2009; Risch et al., 2009). These meta-analyses have been criticized on the grounds that large studies that get most weight in meta-analyses have the poorest measurement quality of life events and, as a consequence, do not find an effect. Another issue is the time frame across which the NLE are measured. Proximal life events appear to be better predictors of depression than more distal events. We present the results of analyses of the 5-HTTLPR × NLE effect on anxious depression and neuroticism scores in a sample of 1,155 twins and their parents and siblings from 438 families. The interaction effect was tested separately for NLE experienced across the life span and NLE experienced in the past year. There was a significant main effect of NLE on anxious depression and neuroticism, especially when these were experienced in the past year. No interaction with 5-HTTLPR was found for NLE either experienced across the life span or across the past year. Our results support the two recent meta-analyses. Given recent insights from genome wide association studies, it seems more useful to focus on the joint effect of several genes, that are, for example, part of the same biological pathway, in interaction with the environment, than on one candidate gene. [ABSTRACT FROM AUTHOR]

This article concerns the power of various data analytic strategies to detect the effect of a single genetic variant (GV) in multivariate data. We simulated exactly fitting monozygotic and dizygotic phenotypic data according to single and two common factor models, and simplex models. We calculated the power to detect the GV in twin 1 data in an ANOVA of phenotypic sum scores, in a MANOVA, and in exploratory factor analysis (EFA), in which the common factors are regressed on the genetic variant. We also report power in the full twin model, and power of the single phenotype ANOVA. The results indicate that (1) if the GV affects all phenotypes, the sum score ANOVA and the EFA are most powerful, while the MANOVA is less powerful. Increasing phenotypic correlations further decreases the power of the MANOVA; and (2) if the GV affects only a subset of the phenotypes, the EFA or the MANOVA are most powerful, while sum score ANOVA is less powerful. In this case, an increase in phenotypic correlations may enhance the power of MANOVA and EFA. If the effect of the GV is modeled directly on the phenotypes in the EFA, the power of the EFA is approximately equal to the power of the MANOVA. [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]

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]

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]

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]

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]

Human height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1,521] polymorphisms). We genotyped large Caucasian samples from Australia (N = 3,906) and the Netherlands (N = 1,689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3 cm) to the effect observed in the published adult meta-analysis. An effect of this size explains approximately 0.1% of the phenotypic variance in height - this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height. [ABSTRACT FROM AUTHOR]

Although life events are often conceptualized as reflecting exogenous risk factors for psychopathology, twin studies have suggested they are heritable. We undertook a mixed twin/adoption study to further explore genetic and environmental contributions to individual differences in the experience of life events. Specifically, a sample of 618 pairs of like-sex adolescent twins, 244 pairs of like-sex adopted adolescent and young adult siblings, and 128 pairs of like-sex biological siblings completed a life events interview. Events were classified as independent (not likely to have been influenced by respondent's behavior), dependent (likely to have been influenced by respondent's behavior), or familial (experienced by a family member), and then summed to form three life event scales. Variance on the scales was assumed to be a function of four factors: additive genetic effects (a2), shared environmental effects (c2), twin-specific effects (t2), and nonshared environmental effects (e2). Data were analyzed using standard biometrical models. Shared environmental effects were found to be the largest contributor to variance in familial events (c2 = .71; 95% confidence interval of .65, .76); additive genetic effects were the largest contributor to dependent events (a2 = .45; CI = .31, .58); and nonshared environmental effects were found to be the largest contributor independent events (e2 = .57; CI = .51, .64). A significant twin-specific effect was also found for independent life events, indicating that twins are more likely to be exposed to such events than non-twin biological siblings. Findings are discussed in terms of their implication for understanding the nature of psychosocial risk. [ABSTRACT FROM AUTHOR]

We examine the heritability of psychological resilience among US adults aged 25 to 74 years. Using monozygotic and same sex dizygotic twin pairs from the National Survey of Mid-Life Development in the United States (MIDUS) we show that positive affect is equally heritable among men (h2 = .60) and women (h2 = .59). We then estimate the heritability of positive affect after controlling for an exhaustive list of social and inter-personal stressors, and we operationalize the residual for positive affect as resilience. According to this specification, the heritability of resilience is higher among men (h2 = .52) compared to women (h2 = .38). We show that self-acceptance is one of the most important aspects of psychological functioning that accounts for the heritability of resilience among both men and women. However, compared to women, men appear to derive additional benefits from environmental mastery that may enable otherwise sex-neutral resilient tendencies to manifest. [ABSTRACT FROM AUTHOR]

We expand our previous deterministic power calculations by calculating the required sample size to detect C in ACE models. The theoretical expected value of the maximum log-likelihood for the AE model was derived using two optimisation methods and these gave near-identical results. Theoretical predictions were verified by computer simulation and the results agreed very well. We have developed a user-friendly web-based tool, TwinPower, to perform power calculations to detect either A or C for the classical twin design. This new tool can be found at http://genepi.qimr.edu.au/cgi-bin/twinpower.cgi. [ABSTRACT FROM AUTHOR]

Previous studies indicate that the emotional quality of marital relationships is mirrored in parent-child relationships. We explored the degree to which these associations are explained by genetic and environmental factors. Participants were drawn from the Twin and Offspring Study in Sweden (TOSS), and included 544 female twin pairs (258 monozygotic [MZ], 286 dizygotic [DZ]), and 311 male twin pairs (128 MZ, 183 DZ). The spouses and one adolescent child of each twin also participated in this study. The twins completed self-report measures that assessed their marital quality and their warmth and negativity towards their children. Observational ratings of marital warmth and negativity, and of maternal warmth and negativity were obtained for a subset of female twin pairs (150 MZ, 176 DZ). Self-reported marital satisfaction was associated with self-reported parental warmth and negativity for mothers (rs = .25, -.36) and fathers (rs = .25, -.44). For the observational measures, marital warmth was associated with maternal warmth (r = .42), while marital negativity was associated with maternal negativity (r = .34). On average genetic factors explained nearly half of the covariance between self-reported marital satisfaction and parenting for mothers (48%) and fathers (47%). Genetic factors explained 21% of the covariance between observed marital and maternal warmth, but did not contribute to associations between marital and maternal negativity. These findings indicate that parents' genetically influenced characteristics help shape the emotional climate of the family. [ABSTRACT FROM AUTHOR]

The physiological benefits of vigorous exercise are well established. The existence of psychological benefits is less clear, however, due to methodological limitations common to investigatory studies. Two of these limitations are the difficulty of establishing appropriate control groups and the large variety of highly specific measures of psychological function available for consideration of effects. To address these limitations, we identified 63 pairs of monozygotic twins from the National Survey of Midlife Development in the United States who were discordant for the amount of vigorous exercise in which they engaged regularly. The twins who regularly engaged in vigorous exercise experienced greater positive psychological functioning than their nonexercising co-twins as measured by the latent factor representing the variance common to 8 measures of mood, optimism, control over life, and interpersonal aspects of personality. The magnitude of the difference was in excess of .4 standard deviations. [ABSTRACT FROM AUTHOR]

From conception to death, helping relationships promote positive development and enable people to surmount challenges in their lives. Is it the case that the negative consequences of a genetic propensity for risky behaviors can be attenuated by helping relationships (a G x E)? But is it also the case that people with such a genetic propensity are less likely to have helping relationships compared to people without such a propensity (a rGE)? We illustrate this complex pattern of gene-environment interplay by drawing on the National Longitudinal Study of Adolescent Health and a combinatoric analytic strategy. We focus on a gene associated with dopamine receptor type 2 (DRD2 TaqIA), student-mentor relationships, and educational continuation beyond secondary school. Results reveal that, for both white and black males, DRD2 A1+ (A1A1 and A1A2 genotypes) is associated with a decreased likelihood of school continuation compared to their counterparts with DRD2 A1-; mentors who are teachers compensate for this negative association (a G x E); and youth with DRD2 A1+ are less likely to have a mentor who is a teacher than their counterparts with DRD2 A1- (a rGE). [ABSTRACT FROM AUTHOR]

Although social and intellectual engagement have been consistently associated with late-life functioning, rather than true causation, these associations may reflect the experiential choices of high functioning individuals (i.e., selection effects). We investigated the association of social activity with late-life physical functioning, cognitive functioning, and depression symptomatology using data from 1112 pairs of like-sex twins who participated in the Longitudinal Study of Aging Danish Twins. Consistent with previous research, we found that social activity was significantly correlated with overall level of physical functioning, cognitive functioning, and depression symptomatology. We also found that social activity was significantly and moderately heritable (estimate of .36), raising the possibility that its association with late-life functioning might reflect selection processes. Further, social activity did not predict change in functioning and in monozygotic twin pairs discordant on level of social activity, the more socially active twin was not less susceptible to age decreases in physical and cognitive functioning and increases in depression symptomatology than the less socially active twin. These results are interpreted in the context of the additional finding that nonshared environmental factors, although apparently not social activity, are the predominant determinant of changes in late-life functioning. [ABSTRACT FROM AUTHOR]

The possibility of genotype-environment interaction for memory performance and change was examined in 150 monozygotic (MZ) twin pairs from the Swedish Adoption Twin Study of Aging (SATSA). We used an MZ twin pair difference approach to examine the possibility that genotype was associated with intrapair variability and thus suggestive of genotype-nonshared environment interactions. Multiple 'variability genes' were found for longitudinal change in a semantic memory task including candidates coding for apolipoprotein E (APOE) and estrogen receptor alpha (ESR1) as well as serotonin candidates (HTR2A and 5HTT). One candidate also related to variability in change in episodic memory (5HTT). Of the significant associations observed, generally results indicated that MZ pairs who carry putative risk alleles were less variable than noncarriers, suggesting that noncarriers may be more sensitive to environmental contexts. We sought to 'contextualize' the possible nonshared environmental influences for found gene-environment (G x E) effects by considering intrapair differences in measured social and stress factors, including social support, life events and depressive symptoms. Results suggested that nonshared environmental influences associated with depressive symptoms may moderate the G x E relationship observed for ESR1 and APOE and longitudinal semantic memory change whereby noncarriers of putative risk alleles may be relatively more sensitive to depressionevoking environmental contexts than carriers of the risk allele. Thus, the contexts that facilitate or reduce depressive symptoms may affect semantic memory resiliency dependent on genotype. Further work ought to consider larger sample sizes as well as consider additional social and contextual factors. [ABSTRACT FROM AUTHOR]

The Wisconsin Twin Panel utilizes the resources of state birth records to study the etiology and developmental course of early emotions, temperament, childhood anxiety and impulsivity, the autism spectrum, and related psychobiological and behavioral phenotypes. The panel currently supports 5 active research studies which involve twins from birth to early adolescence. A range of research methods are employed, including questionnaires and structured interviews with caregivers, home and laboratory-based behavioral batteries, observer ratings, child self-report, psychophysiology, neuroendocrine measures, birth records, genotyping, and cognitive testing. The panel is in the early stages of generating longitudinal findings. [ABSTRACT FROM AUTHOR]

This article describes the design and data availability for samples of genetic pairs in the National Longitudinal Study of Adolescent Health (Add Health). Add Health provides unique samples of genetic pairs that are nationally representative and followed longitudinally from early adolescence into young adulthood with 3 in-home interviews and a 4th interview planned for 2007 to 2008. The design of Add Health included an embedded genetic sample of more than 3000 pairs of individuals with varying genetic resemblance, including monozygotic twins, dizygotic twins, full siblings, half siblings, and unrelated siblings who were raised in the same household. Add Health has collected rich longitudinal social, behavioral, and environmental survey data, as well as buccal cell DNA from a subsample of the genetic sample (N = 2612). Add Health has an enlightened dissemination policy and to date has released phenotype and genotype data to more than 3000 researchers in the scientific community. [ABSTRACT FROM AUTHOR]

The Vietnam Era Twin Study of Aging (VETSA) is a large-scale investigation of cognitive aging from middle to later age. The intended sample of 1440 twin subjects is recruited from the Vietnam Era Twin Registry (VETR), a registry of middle-aged male-male twin pairs who both served in the military during the Vietnam conflict (1965-1975). VETSA employs a multitrait multimethod approach to cognitive assessment to focus on the genetic and environmental contributions to cognitive processes over time, as well as the relative contributions to cognitive aging from health, social, personality, and other contextual factors. The cognitive domains of episodic memory, working memory, abstract reasoning, and inhibitory executive functioning are assessed through neuropsychological testing. In addition, VETSA obtains the participant's score on the Armed Forces Qualification Test, taken at the time of induction into the military around age 20 years, and re-administers the test. Two other projects--VETSA Cortisol and VETSA Magnetic Resonance Imaging--are also in progress using subsamples of the VETSA twins. Prior waves of data collection by VETSA investigators using the VETR have provided historical data on physical and mental health, while future waves of VETSA data collection are planned every 5 years. These methods will provide data on multiple phenotypes in the same individuals with regard to genetic and environmental contributions to cognitive functioning over time, personality and interpersonal risk and protective factors, stress and cortisol regulation, and structural brain correlates of aging processes. [ABSTRACT FROM AUTHOR]

The Colorado Twin Registry (CTR) is a population-based registry housed at the Institute for Behavioral Genetics, University of Colorado. Recruited subjects' birth years date from 1968. Four samples comprise the CTR: the Community Twin Sample, Infant Twin Sample, Longitudinal Twin Sample, and the Early Reading Development Sample. Criteria for enrollment, recruitment strategies, demographic information and zygosity assignment are explained for each sample. In addition, 8 studies in which CTR twins have participated are highlighted. These include studies of early cognition, early reading ability, executive cognitive function, and vulnerability to substance abuse and antisocial behavior. Goals, measures, and brief results are provided for each study. The development of the CTR is an ongoing and evolving process, and it has proved to be a valuable resource, relatively representative of the population from which it was drawn. [ABSTRACT FROM AUTHOR]

The Southern California Twin Register was initiated in 1984 at the University of Southern California, and continues to grow. This article provides an update of the register since it was described in the 2002 special issue of this journal. The register has expanded considerably in the past 4 years, primarily as a result of recent access to Los Angeles County birth records and voter registration databases. Currently, this register contains nearly 5000 twin pairs, the majority of whom are school age. The potential for further expansion in adult twins using voter registration records is also described. Using the Los Angeles County voter registration database, we can identify a large group of individuals with a high probability of having a twin who also resides in Los Angeles County. In addition to describing the expansion of register, this article provides an overview of an ongoing investigation of 605 twin pairs who are participating in a longitudinal study of behavioral problems during childhood and adolescence. Characteristics of the twins and their families are presented, indicating baseline rates of conduct problems, depression and anxiety disorders, and attention-deficit/hyperactivity disorder diagnoses which are comparable to non-twins in this age range. [ABSTRACT FROM AUTHOR]