While evidence supporting for nonadditive genetic influences on personality traits in Caucasian populations has been growing in recent years, twin studies that explored the existence of genetic nonadditivity in personality variation in Asian populations are still lacking. Seven hundred and sixty-five pairs of adolescent and young adult twins registered with the South Korean Twin Registry completed the 7 scales of the Eysenck Personality Scales through a mail survey. Maximum likelihood twin correlations were computed and model-fitting analyses were conducted. Monozygotic twin correlations were consistently higher than twice the dizygotic twin correlations for all 7 scales, suggesting pervasive influences of nonadditive genetic effects on personality traits in the South Korean population. Model-fitting analyses indicated that genetic nonadditivity is particularly important for the variation of Impulsivity, Venturesomeness, Empathy, Lie, and Psychoticism. According to the best fitting models, nonadditive genetic effects ranged from 34 to 49% for these scales. For Neuroticism and Extraversion, models that included an additive genetic component fit better than those including a nonadditive genetic variance component.

We describe the data being collected from the Brisbane Longitudinal Twin Study in Australia as part of the US National Institute on Drug Abuse (NIDA)-funded project, Pathways to Cannabis Use, Abuse and Dependence. The history, recruitment, assessment, and retention of twin families in this project are described in detail, along with preliminary findings and plans for future research. The goal of this NIDA project is to make a significant contribution to the discovery of quantitative trait loci influencing cannabis use disorders. Although the focus is cannabis use, abuse, and dependence in young adults, measures of comorbid illicit drug use disorders are also being collected. In addition, a variety of internalizing and externalizing disorders are being assessed, funded by support from the Australian National Health and Medical Research Council. Because these same twins have participated in numerous twin studies since 1992, future plans will include linking different phenotypes to investigate relationships between drug use, psychiatric disorders, and psychological phenotypes within cross-sectional and longitudinal or developmental frameworks.

Do twins have a lower mean IQ score than singletons? Previous studies have not examined whole populations and are likely to be biased. Twin data from two whole-population surveys of IQ at age 11 years were examined: the Scottish Mental Surveys of 1932 and 1947. Additional variables from childhood were examined as possible mediating effects. There were 1080 twins from the 1932 survey, and 949 from the 1947 survey. In both surveys twins scored lower on the Moray House Test of verbal reasoning, equivalent to a deficit of about 5 IQ points. In the Scottish Mental Survey of 1947 the whole-population group of twins was compared in detail with a representative population sample. The same mental ability difference of about 5 IQ points was found, and was not accounted for by father's occupation, overcrowding in the childhood home, childhood height, school attendance or the number of people in the family.

Current early diagnosis, surveillance and intervention options make it hard to determine the natural course of twin pregnancies, especially regarding spontaneous preterm delivery and perinatal mortality. We studied the natural course in monochorionic (MC) and dichorionic (DC) twin pregnancies in a historical cohort. Twin pregnancies were studied in a unique database of 651 twin pairs born in the period 1907 to 1938. We examined the effect of chorionicity on gestational age, birthweight, peri-natal mortality, intertwin birthweight differences, the incidence of preeclampsia and maternal mortality. Perinatal mortality was 27.7% for MC and 15.8% for DC twins (p < .001). Gestational age and birthweight were stronger predictors of perinatal mortality than chorionicity. Perinatal outcome was poorer for the second twin, especially in DC twins. Delivery before 37 weeks of gestation occurred more often in MC twin pregnancies (48.8% compared to 33.3% in DC twin pregnancies). DC twins were on average 288 g (95% confidence interval 201–376) heavier than MC twins. Severe birthweight discordancy occurred equally in MC and DC twins (18.1%). However, if present, mortality was only increased in MC twins. The birthweight of girls was not affected by the presence of a male co-twin. In this historical cohort MC twin pregnancies had a higher perinatal mortality, caused by a high incidence of low birthweight mainly due to preterm delivery. Mortality did not differ in deliveries after 31 weeks of gestation, which is in contrast to recent data. Apparently, modern obstetrics is more effective in reducing mortality in DC twins.

The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.

The aim of this research was to study fetal and infant mortality in Sweden between 1973 and 1996 in twins vs singletons in relation to gestational duration. Analysis was of fetal and infant mortality based on the number of pregnancies at risk as the denominator rather than the number of deliveries each week. The analysis was based on information stored at the Medical Birth Registry (MBR), the National Board of Health and Welfare, Stockholm. The MBR keeps records on virtually all pregnancies (> 99%) regarding delivery and neonatal information, and for infant mortality up to 1 year of age. During the study period, 2,206,738 singleton and 52,658 twin births were registered. Risk evaluation was made as odds ratio (OR) with a 95% confidence interval. The material was stratified according to parity, maternal age, year of delivery, and delivery unit. Results showed the OR for twin births before 34 weeks gestation was 6 to 8-fold increased compared with singletons. The OR for fetal mortality was increased in all gestational weeks, and like-sexed twins had a consistently poorer prognosis compared to unlike-sexed. Between 1989–96, unlike-sexed twins had a fetal mortality approaching that of singletons. In conclusion, real progress in reduction of infant mortality in twins may be impossible until the high incidence of preterm births can be decreased. Hypothetically, about 100 twin labors would have to be induced to avoid one fetal death in like-sexed twin pregnancies.

Limited data is available that estimates the effect of gestational weight gain on maternal and neonatal outcomes in term twin pregnancies in obese women. A historical cohort study of 831 obese (BMI ≥30.0 kg/m2) women in Missouri delivering 1,662 liveborn, term (≥37 weeks gestation) twin infants in 1998–2005 was conducted. Three gestational weight gain categories were examined: <25 pounds, 25–42 pounds, and >42 pounds. Adjusted odds ratios were calculated with multiple logistic regression, using the 2009 Institute of Medicine provisional guideline of 25–42 pounds as the reference group. Significant increasing trends with gestational weight gain were found for preeclampsia (p < .05), larger twin birth weight (p < .01), smaller twin birth weight (p < .001), and infants weighing >2,500 grams (p < .001). Significant increasing trends for preeclampsia and for cesarean delivery were found in concordant twin pairs (smaller twin >80% of birth weight of larger twin). Women who gained >42 pounds had a borderline significantly higher odds of preeclampsia than women who gained 25–42 pounds (adjusted OR 1.72; 95% CI 1.00–2.99, p = .052). No significant differences were found for 1-min Apgar score <4, 5-min Apgar score <7, or infant mortality ≤1 year. Our study suggests that increasing gestational weight gain is associated with larger infants but increased risk of preeclampsia and cesarean delivery in term twin pregnancies in obese women. Limiting gestational weight gain could reduce the risk of preeclampsia and cesarean delivery. Prospective studies of other study populations and maternal/infant outcomes are needed to evaluate the efficacy of the Institute of Medicine guideline.

Twin registers are wonderful research resources for research applications in medical and behavioral genetics, epidemiology, psychology, molecular genetics, and other areas of research. New registers continue to be launched all over the world as researchers from different disciplines recognize the potential to boost and widen their research agenda. In this article, we discuss multiple aspects that need to be taken into account when initiating a register, from its preliminary sketch to its actual development. This encompasses aspects related to the strategic planning and key elements of research designs, promotion and management of a twin register, including recruitment and retaining of twins and family members of twins, phenotyping, database organization, and collaborations between registers. We also present information on questions unique to twin registers and twin-biobanks, such as the assessment of zygosity by SNP arrays, the design of (biomarker) studies involving related participants, and the analyses of clustered data. Altogether, we provide a number of basic guidelines and recommendations for reflection when planning a twin register.

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.

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.

The Wisconsin Twin Panel is based on the population of all twins born in the state of Wisconsin, United States. Our research focus is the etiology and developmental course of early emotions, temperament, childhood anxiety and impulsivity, the autism spectrum, auditory and tactile sensory sensitivity, and related psychobiological and behavioral phenotypes. We employ a range of research methods including structured interviews with caregivers, observer ratings, child self-report, home-based behavioral batteries, biological measures of basal and reactive cortisol, palm prints, birth records, genotyping, cognitive testing, and questionnaires. Reported results highlight the utility of employing multiple modes of assessment when studying child development and psychopathology.

Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene–environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P = 3.98 × 10−8). We followed up the association in further genotyped monozygotic twins (N = 1,261), which showed a moderate association for the variant (P = 0.200, same direction of an effect). In addition, we report a new association on the level of apolipoprotein A-II (P = 4.03 × 10−8).

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.

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.

Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood, and suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.

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.

Since its start as a database of ‘possible twins’, the Italian Twin Register has developed remarkably in terms of twin approach and recruitment, data-management tools, the cohorts enrolled, and the breadth of information gathered, making the Italian Twin Register a valuable resource for genetic epidemiological research. The Italian Twin Register is a random population of twins at both the national level and within targeted geographical areas or birth cohorts. Further, the Register is linked with disease records and has recently implemented a web-based method for volunteer twin recruitment specifically designed to promote the Register and to disseminate information on genetic epidemiology. To date, approximately 9000 twins have joined the Italian Twin Register, the majority of whom (approximately 70%) represent young adults aged 20 at time of enrolment. Although the total number of twins recruited to date is far below the expected figure initially predicted, the newly established standardized procedures guarantee an increase of around 2000 twins each year. Following the collaboration between the Italian Twin Register and the main Italian nonprofit association for blood donors, twin DNA sampling and storage has recently accelerated contributing to the large amount of phenotypic data collected. The Italian Twin Register is currently involved in both population and clinical based studies on various complex pheno-types and diseases, some conducted within large European consortia.

Twins compared with singletons and monozygous (MZ) compared with dizygous (DZ) twins are at increased risk of fetal and infant death, cerebral palsy and many congenital anomalies. The aim of this study is to investigate whether zygosity is a risk factor for the sudden infant death syndrome (SIDS). Birth registration data and draft infant death certificates for all multiple births in England and Wales 1993 to 2003 were provided by the Office for National Statistics. As a partial proxy for zygosity, same-sex was compared with opposite-sex twins for birthweight-specific mortality and mortality attributed to SIDS. Data on singleton infants were obtained by subtraction of multiple births from routinely published population births and infant deaths. SIDS mortality among low birthweight infants was significantly less in twins than singletons. The twin-singleton relative risk was reversed in infants of normal birthweight. Among infants of normal birthweight, neonatal SIDS was significantly more common in same- compared with opposite-sex pairs. Among infants of low birthweight, postneonatal SIDS was significantly more common in same- compared with opposite-sex pairs. The difference in birthweight distribution of same- compared with opposite-sex twins for neonatal SIDS suggests that zygosity is a risk factor for SIDS. As congenital cerebral anomalies are a feature of many monozygous twin conceptions, a detailed macro- and microscopical examination of the brain in twin SIDS may indicate an otherwise unrecognised pathology.

Increased prenatal exposure to testosterone (T) in females of an opposite-sex (OS) twin pair may have an effect on the development of sex-typical cognitive and behavioral patterns. The prenatal exposure to T due to hormone transfer in OS twin females may occur in two ways, one directly via the feto–fetal transfer route within the uterus, the other indirectly through maternal–fetal transfer and based in the maternal–fetal compartment. Although some studies in singletons indeed found that women pregnant with a male fetus have higher T levels during gestation than women pregnant with a female fetus, many other studies could not find any relation between the sex of the fetus and maternal serum steroid levels. Therefore at present it is unclear whether a pregnant woman bearing a male has higher levels of T than a woman bearing a female. Up to this point, no-one has investigated this issue in twin pregnancies. We examined the relationship between maternal serum steroid levels and sex of fetus in 17 female–female, 9 male–male and 29 OS twin pregnancies. No differences were observed between the maternal serum steroid levels of women expecting single-sex and mixed-sex offspring. It is concluded that the source of prenatal T exposure in females probably comes from the fetal unit, which is the direct route of fetal hormone transfer.

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.