Adolescents' evaluations of family functioning may have a significant impact on their subjective well-being and adjustment. The aim of the study was to investigate the degree to which genetic and environmental influences affect variation in evaluations of general family functioning, family conflict, and quality of life and the overlap between them. We assessed whether genetic and environmental influences are moderated by parental divorce by analyzing self-report data from 6,773 adolescent twins and their non-twin siblings. Genetic, shared, and nonshared environmental influences accounted for variation in general family functioning and family conflict, with genetic influences being relatively more important in girls than boys in general family functioning. Genetic and nonshared environmental influences accounted for variation in quality of life, with genetic influences being relatively more important in girls. Evidence was found for interaction between genetic factors and parental divorce: genetic influence on general family functioning was larger in participants from divorced families. The overlap between general family functioning and quality of life, and family conflict and quality of life was accounted for the largest part by genetic effects, with nonshared environmental effects accounting for the remaining part. By examining the data from monozygotic twins, we found evidence for interaction between genotype and nonshared, non-measured, environmental influences on evaluations of general family functioning, family conflict, and quality of life.

We examined whether externalizing problem behaviors (hyperactivity–impulsivity, aggressiveness, and inattention) predict illicit drug use independently, or whether their associations with drug use are mediated through cigarette smoking. We used a prospective longitudinal design within the FinnTwin12-17 study among Finnish adolescents with baseline at age 12 and follow-up surveys at ages 14 and 17. Path models were conducted with Mplus and included 1992 boys and 2123 girls. The outcome was self-reported ever use of cannabis or other illicit drugs at age 17. The predictors were: externalizing behaviors (hyperactivity–impulsivity, aggressiveness, and inattention) assessed by teachers and parents (age 12) and self-reported cigarette smoking (age 14). The findings differed across behavior studied. The association of hyperactivity–impulsivity with drug use was mostly mediated through earlier cigarette smoking. Concerning aggressiveness and inattention, the results were different among girls than boys. Among girls no significant mediation occurred, whereas among boys more consistent evidence on mediation was seen. Consistently in all models, the direct association of early cigarette smoking on drug use was strong and highly significant. We conclude that the associations of externalizing problem behaviors with illicit drug use are partially mediated through cigarette smoking. Although interventions targeting externalizing problem behaviors may protect adolescents from early onset smoking and subsequently experimenting with drugs, interventions to prevent cigarette smoking initiation are also important in reducing risk of later drug use.

Optimism has a positive influence on mental and somatic health throughout lifetime and into old age. This association is mainly due to shared genetic influences, with some indication of sex differences in the heritability of these and related traits (e.g., depression and subjective wellbeing). Here we extend our initial study of Australian twins by combining with data available from Swedish twins, in order to increase the power to explore potential sex differences in the genetic architecture of optimism, mental and self-rated health and their covariation. Optimism, mental, and self-rated health were measured in 3053 Australian (501 identical female (MZf), 153 identical male (MZm), 274 non-identical female (DZf), 77 non-identical male (DZm), and 242 non-identical opposite-sex twin pairs, and 561 single twins; mean age 60.97 ± 8.76), and 812 Swedish (71 MZf, 53 MZm, 93 DZf and 67 DZm twin pairs, and 244 single twins; mean age 60 ± 14.3) twin individuals using the Life Orientation Test (LOT), the General Health Questionnaire (GHQ) and a single-item self-rating of overall health, respectively. In females all three traits were moderately heritable (.27–.47), whereas in males heritability was substantially lower (.08–.19), but genetic modeling showed that sex differences were not significant. The absence of significant sex differences, despite the consistent trend across the two cohorts, is likely due to a lack of power, raising the importance for future studies, on the same or similar traits, to utilize large samples and to keep the possibility of sex differences in mind when conducting their analyses.

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.

This study investigated phenotypic correlations between mental toughness and humor styles, as well as the common genetic and environmental effects underlying these correlations. Participants were 201 adult twin pairs from North America. They completed the Humor Styles Questionnaire, assessing individual differences in two positive (affiliative, self-enhancing) and two negative (aggressive, self-defeating) humor styles. They also completed the MT48, measuring individual differences in global mental toughness and its eight factors (Commitment, Control, Emotional Control, Control over Life, Confidence, Confidence in Abilities, Interpersonal Confidence, Challenge). Positive correlations were found between the positive humor styles and all of the mental toughness factors, with all but one reaching significance. Conversely, negative correlations were found between all mental toughness factors and the negative humor styles, with the mental toughness factors of Control, Emotional Control, Confidence, Confidence in Abilities, and Interpersonal Confidence exhibiting significant correlations. Subsequent behavioral genetic analyses revealed that these phenotypic correlations were primarily attributable to common genetic and common non-shared environmental factors. The implications of these findings regarding the potential effects of humor styles on wellbeing, and the possible selective use of humor by mentally tough individuals are discussed.

Individuals who experience one type of trauma often experience other types, yet few studies have examined the clustering of trauma. This study examines the clustering of traumatic events and associations of trauma with risk for single and co-occurring major depressive disorder (MDD) and panic attack for 20 years after first trauma. Lifetime histories of MDD, panic attack, and traumatic events were obtained from participants in an Australian twin sample. Latent class analysis was used to derive trauma classes based on each respondent's trauma history. Associations of the resulting classes and of parental alcohol problems and familial effects with risk for a first onset of single and co-occurring MDD and panic attack were examined from the year of first trauma to 20 years later. Traumatic events clustered into three distinct classes characterized by endorsement of little or no trauma, primarily nonassaultive, and primarily assaultive events. Individuals in the assaultive class were characterized by a younger age at first trauma, a greater number of traumatic events, and high rates of parental alcohol problems. Members of the assaultive trauma class had the strongest and most enduring risk for single and co-occurring lifetime MDD and panic attack. Assaultive trauma outweighed associations of familial effects and nonassaultive trauma with risk for 10 years following first trauma.

We analyzed depressive and psychosomatic symptoms in relation to co-twin dependence in 419 twins at the age of 22 to 30 years. Depressive symptoms were assessed, as previously, with Children's Depression Inventory modified to be suitable for this age and reported as a total score and three subscales (low self-confidence, anhedonia and sadness) based on factor analysis as reported in a previous epidemiological study conducted in Finland. Items assessing nervous complaints and somatic symptoms were adapted from Finnish studies of juvenile health habits. Inter-twin dependence decreased with increasing age in both genders. Monozygotic twins, especially monozygotic females, reported most often to be dependent on their co-twin. When the symptom reporting was evaluated in relation to co-twin dependence, no relation was found between co-twin dependence and depressive symptom reporting. However, dependence-independence imbalance within twin pair was associated with elevated levels of depressive and psychosomatic symptoms, especially in twins who perceived themselves as dependent and the co-twin as independent. We conclude that there was no relation found between co-twin dependence and depressive symptom reporting in male and female twins except for the few imbalance cases, where most symptoms were reported by those dependent twins who felt their co-twin as independent.

Bread is an elementary part of the western diet, and especially rye bread is regarded as an important source of fibre. We investigated the heritability of eating bread in terms of choice of white and rye bread and use-frequency of bread in female and male twins in Denmark and Finland. The study cohorts included 575 Danish (age range 18–67 years) and 2009 Finnish (age range 22–27 years) adult twin pairs. Self-reported frequency of eating bread was obtained by food frequency questionnaires. Univariate models based on linear structural equations for twin data were used to estimate the relative magnitude of the additive genetic, shared environmental and individual environmental effects on bread eating frequency and choice of bread. The analysis of bread intake frequency demonstrated moderate heritability ranging from 37–40% in the Finnish cohort and 23–26% in the Danish cohort. The genetic influence on intake of white bread was moderate (24–31%), while the genetic influence on intake of rye bread was higher in men (41–45%) than in women (24–33%). Environmental influences shared by the twins were not significant. Consumption of bread as well as choice of bread is influenced by genetic predisposition. Environmental factors shared by the co-twins (e.g., childhood environment) seem to have no significant effects on bread consumption and preference in adulthood.

The purpose of this study was to examine potential biases in family history reports of problem gambling and gambling frequency. Same-sex twin pairs discordant for a history of problem (n = 230 pairs) and pathological gambling (n = 48 pairs) and for three indexes of gambling frequency (ever gambling, monthly gambling, and weekly gambling; n = 44–517 pairs) were identified from a large Australian national twin study. The problem gambling affected twin was significantly more likely to endorse paternal problem gambling than the problem gambling unaffected cotwin (OR = 5.5), and similar findings were obtained for family history reports of gambling frequency (OR = 2.0–2.8). These results could not be explained by differences between the discordant pairs in whether they had spent time gambling with the parents; there was no association between a history of problem, monthly or weekly gambling and having gambled with the parents among discordant twin pairs. The results of this study suggest that relying solely on family history assessments of disordered gambling and gambling involvement can lead to incorrect estimates of the strength of the family history effect.

The objective of the current study was to investigate the heritability of breast size and the degree to which this heritability is shared with BMI. In a sample of 1010 females twins (mean age 35 years; SD = 2.1; range 28–40), self-report data pertaining to bra cup size and body mass index (BMI) was collected in the context of self-report data and an interview relating to disordered eating respectively. In a sample of 348 complete twin pairs who completed data collection (226 MZ pairs and 122 DZ pairs and 360 incomplete pairs (170 MZ and 190 DZ)), we found that the heritability of bra cup size was 56%. Of this genetic variance, one third is in common with genes influencing body mass index, and two thirds (41% of total variance) is unique to breast size, with some directional evidence of non-additive genetic variation. The implications of these findings with respect to previous research linking breast size with reproductive potential are discussed.

The present study investigated the location of trait emotional intelligence (trait EI or trait emotional self-efficacy) within the context of the HEXACO model — a more comprehensive personality framework than the conventional Big Five structure. A total of 666 MZ and 526 DZ adult twin pairs from the United Kingdom completed the short form of the Trait Emotional Intelligence Questionnaire (TEIQue-SF) and the short form of the HEXACO Personality Inventory (HEXACO-60). Many significant phenotypic correlations between the TEIQue-SF and the HEXACO-60 were obtained, which were strongest for HEXACO Extraversion, and weakest for HEXACO Honesty–Humility. As was expected, Emotionality was the only HEXACO dimension to correlate negatively with TEIQue-SF scores. Bivariate behavioral genetic analyses revealed that all phenotypic correlations were attributable to common genetic and common nonshared environmental factors. The study confirms the validity of trait EI as a constellation of emotional self-perceptions located at the lower levels of personality.

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting females almost exclusively and is characterized by a wide spectrum of clinical manifestations. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene have been found in up to 95% of classical RTT cases and a lesser proportion of atypical cases. Recently, mutations in another X-linked gene, CDKL5 (cyclin-dependent kinase-like 5) have been found to cause atypical RTT, in particular the early onset seizure (Hanefeld variant) and one female with autism. In this study we screened several cohorts of children for CDKL5 mutations, totaling 316 patients, including individuals with a clinical diagnosis of RTT but who were negative for MECP2 mutations (n = 102), males with X-linked mental retardation (n = 9), patients with West syndrome (n = 52), patients with autism (n = 59), patients with epileptic encephalopathy (n = 33), patients with Aicardi syndrome (n = 7) and other patients with intellectual disability with or without seizures (n = 54). In all, seven polymorphic variations and four de novo mutations (c.586C>T [p.S196L]; c.58G>C [p.G20R]; c.2504delC [p.P835fs]; deletion of exons 1 - 3) were identified, and in all instances of the latter the clinical phenotype was that of an epileptic encephalopathy. These results suggest that pathogenic CDKL5 mutations are unlikely to be identified in the absence of severe early-onset seizures and highlight the importance of screening for large intragenic and whole gene deletions.

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%.

The aim of this study was to quantify contributions of genetic and environmental factors to variation in timing of emergence of the primary teeth in a sample of monozygotic and dizygotic twins, using univariate model-fitting approaches. The sample comprised 94 pairs of monozygotic twins and 125 pairs of dizygous twins, all of European ancestry, aged from 2–6 years. Tooth emergence timing was based on parental report, with a subset of data validated by clinical assessment. Heritability estimates for tooth emergence timing were generally high, around 90%, however estimates for the lower right lateral incisor and the lower canines were around 50%. These findings confirm a strong genetic influence on observed variation in the timing of emergence of the human primary teeth.

Copy number variations (CNVs) are common structural variations in the human genome that strongly affect genomic diversity and can play a role in the development of several diseases, including neurodevelopmental disorders. Recent reports indicate that monozygotic twins can show differential CNV profiles. We searched CNVs in monozygotic twins discordant for schizophrenia to identify susceptible loci for schizophrenia. Three pairs of monozygotic twins discordant for schizophrenia were subjected to analysis. Genomic DNA samples were extracted from peripheral blood lymphocytes. We adopted the Affymetrix Genome-Wide Human SNP (Single Nucleotide Polymorphism) Array 6.0 to detect copy number discordance using Partek Genomics Suite 6.5 beta. In three twin pairs, however, validations by quantitative PCR and DNA sequencing revealed that none of the regions had any discordance between the three twin pairs. Our results support the hypothesis that epigenetic changes or fluctuation in developmental process triggered by environmental factors mainly contribute to the pathogenesis of schizophrenia. Schizophrenia caused by strong genetics factors including copy number alteration or gene mutation may be a small subset of the clinical population.

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 ∼550,000 genotyped SNPs. We identified a single genome-wide significant variant for height (P value = 1.06 × 10–9) located in HHIP, a well-replicated height-associated gene. Suggestive levels of association were found for other known genes associated with height (P values < 1 × 10–6): ADAMTSL3, EFEMP1, GPR126, and HMGA2; and BMI (P values < 1 × 10–4): FTO and MC4R. Together, these variants explain less than 2% of total phenotypic variation for height and 0.5% for BMI.

The aim of this study is to characterize the relationship between major depression and the metabolic syndrome in a large community based sample of Australian men and women aged 26–90 years. A lifetime history of major depression was assessed by telephone interview following the DSM–III-R. A current history of metabolic syndrome was assessed following the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP AP-III) guidelines 1 to 3 years later. Logistic regression was used to estimate the association between depression and the metabolic syndrome, and its component criteria, controlling for age, sex and alcohol dependence. There was no association between a lifetime history of major depression and the presence of the metabolic syndrome. There was a weak association between depression and low high-density lipoprotein cholesterol but not with other component criteria of the metabolic syndrome. Despite calls for interventions directed at depression to reduce the onset of the metabolic syndrome there are important failures to replicate in large samples such as this, no consensus regarding the threshold at which depression may pose a significant risk even allowing for heterogeneity across populations, and no consensus regarding confounders that may explain inter-study differences. The absence of any dosage effect of depression on the associated risk for the metabolic syndrome in other unselected samples does not support a direct causal relationship. The call for intervention studies on the basis of the currently published evidence base is unwarranted.

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.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by heterozygotic inactivation of the NF1 tumor suppressor gene at 17q11.2. The associated phenotypes are highly variable, and modifying genes have been proposed to explain at least in part the intriguing expressivity. Given that haploinsufficiency of the NF1 gene product neurofibromin is responsible for some of the clinical manifestations, variations in expression of the wildtype NF1 allele might modify the phenotype. We therefore investigated epigenetic molecular modifications that could result in variable expression of the normal NF1 allele. To exclude confounding by DNA sequence variations, we analyzed monozygotic twin pairs with NF1 who presented with several discordant features. We fine-mapped the methylation pattern of a nearly 1 kb NF1 promoter region in lymphocytes of 8 twin pairs. All twin pairs showed significant intra-pair differences in methylation, especially of specific promoter subregions such as 5'UTR, exon 1 and intron 1 (+7 to +622), transcription factor binding sites and promoter elements like NF1HCS. Furthermore, we detected significant intra-pair differences in cytosine methylation for the region from -249 to -234 with regard to discordance for optic glioma with a higher grade of methylation in glioma cases. In conclusion, our findings of epigenetic differences of the NF1 promoter in leukocytes within mono zygotic twin pairs may serve as a proof of principle for other tissues. The results point towards a role of methylation patterns of the normal NF1 allele for expression differences and for modification of the NF1 phenotype.