Research shows that perceived family cohesion is positively related to prosocial behavior in adolescents. In this study, we investigated heritability of prosocial behavior (PB) and perceived family cohesion (FC) among Nigerian twins attending public schools in Lagos State, Nigeria (mean age = 14.7 years, SD = 1.7 years), and explored the issue of whether children's perception of cohesive family environment moderated genetic and environmental influences on (PB). The PB scale of the Strengths and Difficulties Questionnaire and the FC scale of the Family Adaptability and Cohesion Evaluation Scale III were completed by 2,376 twins (241 monozygotic (MZ) male, 354 MZ female, 440 dizygotic (DZ) male, 553 DZ female, and 788 opposite-sex DZ twins). A general sex-limitation and the bivariate genotype by environment interaction (G×E) models were applied to the data. The general sex-limitation model showed no significant sex differences, indicating that additive genetic and non-shared environmental influences were, 38% (95% CI = 31, 46) and 62% (95% CI = 54, 69) for PB and 33% (95% CI = 24, 40) and 67% (95% CI = 60, 76) for FC in both sexes. These estimates were similar to those found in Western and Asian twin studies to date. The correlation between PB and FC was 0.36. The best-fitting bivariate G×E model indicated that FC significantly moderated non-shared environmental influence unique to PB (E×E interaction). Specifically, non-shared environmental contributions to PB were highest when FC was lowest, and decreased as the levels of FC increased. However, genetic variances in PB were stable across all levels of FC. These findings suggest that FC reduces individual differences in PB by changing non-shared environmental experiences rather than genetic factors in PB.

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.

Chorion type is an important variable that can affect the prenatal environment of monozygotic (MZ) twin pairs, leading to differences in growth and development. In particular, vascular anastomoses between monochorionic (MC) MZ twin pairs can lead to an imbalance in nutrition between co-twins. One objective of this study was to determine whether maternal reports, hospital records or birthweight discordances found in MZ co-twins provide reliable indications of monochorionicity. The other objective was to test the hypotheses that in MZ twin pairs of known chorion type, MC twin pairs would show greater birthweight differences and greater within-pair variability in permanent tooth size than dichorionic (DC) twin pairs, reflecting greater differences in intrauterine environment between MC MZ pairs. Birthweights and tooth size data were recorded for 170 pairs of MZ Australian twins enrolled in an ongoing study of dentofacial growth and development. Chorion type based on maternal reports was compared with that based on hospital records for a subsample of 68 pairs of these MZ twins. Maternal reports were found to be unreliable for determining chorion type and hospital records often did not provide enough information to be certain about chorionicity. For 27 twin pairs with confirmed chorion type, associations were tested between birthweight discordances in MZ twin pairs and chorion type, and also between intrapair variances for tooth size and chorion type. A significant association was noted between birthweight discordance and chorion type (p <.05), with greater discordances occurring more often in MC twin pairs. Although significant heterogeneity of intrapair variances for tooth size was found in only 5 of 48 comparisons, intrapair variances for crown dimensions were greater significantly more often in MC pairs than DC pairs (p <.05). Our findings indicated that neither maternal reports nor often hospital records can be relied upon for information on chorion type. However, when analyses were performed on data for MZ twin pairs of known chorion type, we found evidence of a significant association between intrapair birthweight differences and chorion type and also between intrapair variances of dental crown measurements and chorion type. Consistent with our hypotheses, large birthweight discordances were found to occur more often in MC twin pairs than DC twin pairs, and intrapair variances for tooth size in MC twin pairs exceeded those in DC twin pairs more often than expected due to chance.

It has been suggested that twinning may influence handedness through the effects of birth order, intra-uterine crowding and mirror imaging. The influence of these effects on handedness (for writing and throwing) was examined in 3657 Monozygotic (MZ) and 3762 Dizygotic (DZ) twin pairs (born 1893–1992). Maximum likelihood analyses revealed no effects of birth order on the incidence of left-handedness. Twins were no more likely to be left-handed than their singleton siblings (n = 1757), and there were no differences between the DZ co-twin and siblingtwin covariances, suggesting that neither intra-uterine crowding nor the experience of being a twin affects handedness. There was no evidence of mirror imaging; the co-twin correlations of monochorionic and dichorionic MZ twins did not differ. Univariate genetic analyses revealed common environmental factors to be the most parsimonious explanation of familial aggregation for the writing-hand measure, while additive genetic influences provided a better interpretation of the throwing hand data.

The purpose of this study was to examine changes in the contribution of genetic and environmental influences to leisure time physical activity among male and female twins over a 6-year follow-up. At baseline the sample comprised 4,280 monozygotic and 9,276 dizygotic twin individuals, and at follow-up 4,383 monozygotic and 9,439 dizygotic twin individuals. Participants were aged 18–54 years at baseline. Genetic modeling results showed that genetic influences on leisure time physical activity declined from baseline (44%) to follow-up (34%). Most of the genetic influences identified at baseline were present at followup (rg = 0.72). Specific environmental influences increased from baseline (56%) to follow-up (66%) while at follow-up new environmental time-specific influences were observed (re = 0.23). The model with sex differences showed a higher estimate of genetic influences for men than women both at baseline (men 47% vs. women 42%) and at follow-up (men 38% vs. women 31%). The additive genetic correlation for this phenotype was greater for men (rg = 0.79) than women (rg = 0.64). The specific environmental influences were corresponding; at baseline men 53% and women 56% and at follow-up men 62 % and women 69%. The environmental correlations between the two time points were similar for men (re= 0.21) and for women (re= 0.24). In conclusion, in a sample of healthy twins most of the genetic influences on leisure time physical activity expressed at baseline were present at 6 years of follow-up. New specific environmental factors underlying follow-up leisure time physical activity were observed.

The East Flanders Prospective Twin Survey (EFPTS) is a registry of multiple births in the province of East Flanders, Belgium. Since its start in 1964, over 10,000 twin-pairs have been registered. EFPTS has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are recruited at birth; basic perinatal data are recorded; chorion type and zygosity are established; since 1969, placental biopsies have been taken and frozen at –20°C for future research. Since its origin, the EFPTS has included placental data and allows differentiation of three subtypes of monozygotic twins based on the time of the initial zygotic division: the dichorionic–diamniotic pairs (early, with splitting before the fourth day after fertilization), the monochorionic–diamniotic pairs (intermediate, splitting between the fourth- and the seventh-day postfertilization) and the monochorionic–monoamniotic pairs (late, splitting after the eighth day postfertilization). Studies can be initiated taking into account primary biases, those originating ‘in utero’. Such studies could throw new light on the consequences of early embryological events and the gene–environment interactions as far as periconceptional and intrauterine environment are concerned.

The human ACTN3 gene encodes the protein α-actinin-3, a component of the contractile apparatus in fast skeletal muscle fibers. In 1999, we identified a common polymorphism in ACTN3 (R577X) that results in absence of α-actinin-3 in more than one billion people worldwide, despite the ACTN3 gene being highly conserved during human evolution. In 2003, we demonstrated that ACTN3 genotype influences elite athletic performance, and the association between ACTN3 genotype and skeletal muscle performance has since been replicated in athletes and non-athlete cohorts. We have also studied the evolution of the R577X allele during human evolution and demonstrated that the null (X) allele has undergone strong, recent positive selection in Europeans and Asian populations. We have developed an Actn3 knockout mouse model that replicates α-actinin-3 deficiency in humans and has already provided insight into the role of α-actinin-3 in the regulation of skeletal muscle metabolism, fibre size, muscle mass and contractile properties. In particular, mouse muscle lacking α-actinin-3 uses energy more efficiently, with the fast fibers displaying metabolic and contractile properties of slow oxidative fibers. While this favors endurance activities, the trade off is that the muscle cannot generate the rapid contractions needed to excel in sprinting. We propose that the shift towards more efficient aerobic muscle metabolism associated with α-actinin-3 deficiency also underlies the adaptive benefit of the 577X allele. Our future studies will focus on the effect of ACTN3 genotype on response to exercise and ageing, and the onset and severity of muscle disease phenotype.

Twin studies of diabetes mellitus can help elucidate genetic and environmental factors in etiology and can provide valuable biological samples for testing functional hypotheses, for example using expression and methylation studies of discordant pairs. We searched the volunteer Australian Twin Registry (19,387 pairs) for twins with diabetes using disease checklists from nine different surveys conducted from 1980–2000. After follow-up questionnaires to the twins and their doctors to confirm diagnoses, we eventually identified 46 pairs where one or both had type 1 diabetes (T1D), 113 pairs with type 2 diabetes (T2D), 41 female pairs with gestational diabetes (GD), 5 pairs with impaired glucose tolerance (IGT) and one pair with MODY. Heritabilities of T1D, T2D and GD were all high, but our samples did not have the power to detect effects of shared environment unless they were very large. Weight differences between affected and unaffected cotwins from monozygotic (MZ) discordant pairs were large for T2D and GD, but much larger again for discordant dizygotic (DZ) pairs. The bivariate genetic analysis (under the multifactorial threshold model) estimated the genetic correlation between body mass index (BMI) and T2D to be 0.46, and the environmental correlation at only 0.06.

Much progress has been made in twin research since our last special issue on twin registries (Hur, Y.-M., & Craig, J. M. (2013). Twin Research and Human Genetics, 16, 1–12.). This special issue provides an update on the state of twin family registries around the world. This issue includes 61 papers on twin family registries from 25 countries, of which 3 describe consortia based on collaborations of several twin family registries. The articles included in this issue discuss the establishment and maintenance of twin registries, recruitment strategies, methods of zygosity assessment, research aims and major findings from twin family cohorts, as well as other important topics related to twin studies. The papers amount to approximately 1.3 million monozygotic, dizygotic twins and higher order multiples and their family members who participate in twin studies around the world. Nine new twin family registries have been established across the world since our last issue, which demonstrates that twin registers are increasingly important in studies of the determinants and correlates of complex traits from disease susceptibility to healthy development.

This review addresses the physiology of monochorionic diamniotic (MC/DA) twins and the potential for twin–twin transfusion syndrome (TTTS). It focuses on the underlying cardiovascular pathophysiology of TTTS and the cardiovascular impact of TTTS for both the recipient and the donor twin. It explains the principles for assessment and monitoring of these cardiovascular changes and how these may be used to guide pregnancy management. Finally, it describes the effect of treatment on the altered hemodynamics and how this can influence pregnancy and perinatal management, as well as longer-term follow-up.

Estimates suggest up to 15% of multiples grow up as singleton survivors. Few studies have reported how bereaved multiple birth mothers with a surviving multiple cope with their bereavement. Using the population-based Western Australian Twin Child Health study database and other sources, we interviewed 66 bereaved mothers with at least one surviving multiple. For many, this contact was the first acknowledgement of their status as multiple birth mothers since their loss. The Beck Depression Inventory 2nd Edition (BDI) showed significant reduction in depression between the time of loss and our interview. For mothers as a group there was a high correlation between current and retrospective BDI, and retrospective BDI and all three Perinatal Grief Scales (PGS). There was a significant correlation between the three grief factors on the PGS. When subdivided, this held for mothers who suffered a loss at or before the neonatal period, but not for those whose loss occurred later. Bereaved mothers of multiples scored significantly higher on the PGS than the PGS norm for bereaved mothers of singletons, which we attribute to others not acknowledging their grief, and/or recruitment differences. There were no significant differences in PGS scores related to cause, the time since death, or sibling number or age. Spiritual beliefs and finding meaning in loss were positively related to scores for adjustment and acceptance. Although traumatised, most mothers accommodated their losses meaningfully in their lives. Their own support recommendations are included.

We sought to investigate the risk of incident major depressive disorder (MDD) attributable to a range of sleep disorders in the Danish population. Data were obtained by linking longitudinal Danish population-based registers. A total of 65,739 individuals who had first onset of depression between 1995 and 2013 were selected as cases. For each case, a set of 20 controls of the same sex, birth month and year and who had not had depression by the date that the case was diagnosed were selected at random form the population (N = 1,307,580 in total). We examined whether there was an increased rate of prior sleep disorders in MDD cases compared to controls using conditional logistic regression. An increased risk of incident depression in cases was found for all sleep disorders analyzed. Highest incidence rate ratios (IRRs) were found for circadian rhythm disorders (IRR = 7.06 [2.78–17.91]) and insomnia of inorganic origin (IRR = 6.76 [4.37–10.46]). The lowest estimated IRR was for narcolepsy (IRR = 2.00 [1.26–3.17]). Those diagnosed with a sleep disorder in the last 6 months were at highest risk of developing depression compared to those with at least 1 year since diagnosis (3.10 vs. 2.36). Our results suggest that having any sleep disorder is a risk factor for incident depression. Depression screening should be considered for patients with sleep disorders, and where possible, long-term follow-up for mental health problems is advisable.

Previous genetic investigations of variation in normal sleep have focused on measures that describe sleep over longer periods of time. We undertook a study with the aim of evaluating whether heritability can be found in single-night sleep traits. A classical twin study design of monozygotic and dizygotic twins, enriched with siblings of twins was employed. The study included adult twin pairs and their siblings (N = 813 subjects from 342 families). A subsample of 66 individuals participated twice. For a single night, bedtime, awakening time and subjective sleep quality were assessed using a diary. The diary also assessed smoking, alcohol and coffee consumption, and the subjective evaluation of stress. Resemblance between family members was used to estimate the heritability of bedtime, awakening time, sleep problems and sleep quality as a function of sex. Most sleep measures showed familial clustering, but results differed for men and women. Heritability for bedtime and sleep problems was seen in women; and for awakening time in men. We conclude that heritability can be demonstrated for bedtime and subjective evaluation of even a single night of sleep. The contribution of the genetic make-up is sex specific. In women variance in awakening time is so affected by environmental circumstances, that the genetic contribution to the variance becomes negligible. In contrast, for males, variance in the evening bedtime is so affected by environmental circumstances, that the genetic contribution to the variance becomes negligible.

This study examined genetic and environmental contributions to the covariance between aggression and hyperactivity-impulsivity as rated by twins' teachers and parents. Sex-differences in these genetic and environmental contributions and rater bias/sibling interaction effects were of interest as well. Part of an ongoing nation-wide twin-family study of behavioral development and health habits, the sample consisted of 1636 Finnish twin pairs ascertained from five consecutive and complete twin birth cohorts. Data were collected at ages 11–12, using teacher and parental rating forms of the Multidimensional Peer Nomination Inventory. Bivariate analyses were performed using structural equation modeling allowing sex-limitation effects. Results show that, in addition to significant genetic and environmental influences specific to each behavior, aggression and hyperactivity-impulsivity share common genetic and environmental etiology. Results provide evidence that both genetic and environmental factors are important in creating the observed correlation between aggression and hyper-activity-impulsivity.

Problem (P) and pathological gambling (PG) symptoms wax and wane. Past symptoms are a risk for future symptoms even after controlling for familial influences. To address the genetic architecture of lifetime PG and current PG symptoms, we tested for common and unique genetic factors to lifetime PG symptoms at baseline and past year PG symptoms at 10-year follow-up. Diagnostic and Statistical Manual of Mental Disorders (3rd ed., Rev.; DSM-III-R; American Psychiatric Association, 1987) lifetime criteria of one or more PG symptoms were derived in 1992 and past year PG symptoms in 2002 from 1675 individual twins from the Vietnam Era Twin Registry. Cholesky decomposition models were fit to baseline and past year PG symptoms. Under the best fitting model we observed that 49% of the risk for one or more baseline PG symptoms in 1992 was due to a genetic factor and 51% of the risk was due to a unique environmental factor. All of the genetic variance (57.5%) in risk to past year PG symptoms in 2002 was common with baseline PG symptoms. Unique environment accounted for the remaining variance in past year PG symptoms with 13% common to baseline and 30% specific to past year PG symptoms. The genetic contributions to lifetime and past year gambling symptoms 10 years later are similar. There is no evidence for genetic contributions unique to past year PG symptoms. However, most of the unique environmental influences to past year PG are not shared with lifetime PG. This may reflect the changed social–cultural environment between 1992 and 2002, characterized by increasing access to legalized gambling.

Depressive symptoms reflect depressed mood over a relatively short period of time and are measured using symptom checklists such as the SCL-90. There is some evidence that depressive symptoms are associated with major depression (MD), which is a clinically diagnosed psychiatric illness. Genetic studies of depressive symptomatology suggest a role for genetic factors as well as unique environmental influences. While epidemio-logical research suggests that depressive symptoms may be influenced by sex-specific factors, few genetically informative findings support this result entirely. We used data from male and female same-sex and opposite-sex twin pairs to assess the extent to which genetic, shared and unique environmental factors influence depressive symptoms. Furthermore, we tested for the presence of qualitative and quantitative sex differences in depressive symptoms. Our results suggest that similar to other studies, depressive symptomatology is moderately heritable (31%) with no evidence for shared environmental factors. Our best fitting model suggests that there are no qualitative or quantitative sex differences in depressive symptoms. Our analyses suggest that while there may be mean differences in the levels of depressive symptoms across sexes, the genetic and environmental factors that predispose males and females to depressive symptoms are not different.

The Craniofacial Biology Research Group in the School of Dentistry at The University of Adelaide is entering an exciting new phase of its studies of dental development and oral health in twins and their families. Studies of the teeth and faces of Australian twins have been continuing for nearly 30 years, with three major cohorts of twins recruited over that time, and currently we are working with twins aged 2 years old to adults. Cross-sectional data and records relating to teeth and faces of twins are available for around 300 pairs of teenage twins, as well as longitudinal data for 300 pairs of twins examined at three different stages of development, once with primary teeth, once at the mixed dentition stage, and then again when the permanent teeth had emerged. The third cohort of twins comprises over 600 pairs of twins recruited at around birth, together with other family members. The emphasis in this third group of twins has been to record the timing of emergence of the primary teeth and also to sample saliva and dental plaque to establish the timing of colonization of decay-forming bacteria in the mouth. Analyses have confirmed that genetic factors strongly influence variation in timing of primary tooth emergence. The research team is now beginning to carry out clinical examinations of the twins to see whether those who become colonized earlier with decay-forming bacteria develop dental decay at an earlier age. By making comparisons within and between monozygotic (MZ) and dizygotic (DZ) twin pairs and applying modern molecular approaches, we are now teasing out how genetic, epigenetic, and environmental factors interact to influence dental development and also oral health.

This study reports on the determination of zygosity in Chinese adult twins by simple questionnaire and physical features comparison. The subjects were 511 twin pairs from two cities and their town areas, consisting of 371 monozygotic (MZ) and 140 same-sex dizygotic (DZ) pairs, identified by ABO blood group and multiplex polymerase chain reaction of several polymorphic short tandem repeat markers. The twins themselves responded to 8 questionnaire items, 4 items on twin similarity, and 4 items on the frequency of mistaking one twin for another by parents, relatives, teachers and strangers when they were 6 to 13 years old. Research assistants responded to 20 items regarding twins' physical features at the moment of interview. A parsimonious model established using stepwise logistic regression analysis of the 28 items showed that the total accuracy of zygosity diagnosis was 90.1%. The accuracy was 89.2% when using only the items dealing with the confusion of twins and 85.4% using only similarity. In the questionnaire, ‘facial appearance’, ‘mistaken by teachers’ and ‘mistaken by strangers’ had stronger discriminating power between MZ and DZ twins. Two physical features — ‘eyelid’ and ‘middigital hair’ — were informative to some extent. There was no statistically significant sex and area difference in the validity of such questionnaire and physical features comparison-based classification. In conclusion, questionnaire-based zygosity assessment in this Chinese adult twin sample could still be regarded as a valid and valuable classification method. Physical features comparison, however, could only provide limited information for zygosity determination.

Previous analyses in a large population-based sample of female twins indicated that three dimensions of religiosity – personal devotion, personal conservatism and institutional conservatism – were, in different ways, significantly related to current depressive symptoms and substance use and lifetime psychiatric and substance use disorders. Furthermore, personal devotion, but neither personal conservatism nor institutional conservatism, buffered the depressogenic effects of stressful life events (SLEs). We here explore further these results, using linear, logistic and Cox regression models. Eight personality and six demographic variables had distinct patterns of association with the three dimensions. Personal devotion was positively associated with years of education, age, and optimism and negatively correlated with neuroticism. Personal conservatism was negatively associated with education, income, age, mastery and positively correlated with neuroticism. Institutional conservatism was negatively correlated with self-esteem and parental education. Covarying for these 14 variables produced little change in their association with psychiatric and substance use outcomes. The impact of the dimensions of religiosity differed as a function of the SLE category. High levels of both personal devotion and institutional conservatism protected against the depressogenic effects of death and personal illness. High levels of personal conservatism were associated with increased sensitivity to relationship problems. These results suggest that the association between religiosity and low risk for symptoms of depression and substance use may be in part causal. The relationship between dimensions of religiosity and response to SLEs is complex but probably of importance in clarifying the nature of the coping process.

There are a growing number of large-scale initiatives for twin registers of children. The Australian Twin ADHD Project (ATAP) is used to illustrate two key limitations which may arise with such studies, namely (1) the importance of including or possibly excluding families in which one or both twins have significant developmental disability, and (2) the selective failure to recruit and/or the selective attrition of families in which parents and children share behavioral difficulties. Initially ATAP excluded 1 in 6 of families whose twins were enrolled in the volunteer-based Australian Twin Registry (ATR), and as more children with significant problems were identified, these families were sequentially excluded. With longitudinal data over ten years, two points about retention were identified: the difficulty of retaining the twins in late adolescence, and the loss of the families whose twins had more ADHD symptoms. We discuss strategies for limiting the loss of families and for ensuring comparability of data across registers with similar interests but different methods of recruitment and exclusion.