The aim of this study was to determine the genetic contribution to the variation in testosterone and the aggression-hostility-anger (AHA) syndrome in middle-aged twins. Moreover, the relation between testosterone and this syndrome, and possible common genetic mechanisms were investigated. Towards this end, blood samples were collected at two time points; the AHA syndrome was measured using three questionnaires: the Buss-Durkee Hostility Inventory with seven subscales, the Jenkins Activity Survey and the Spielberger State-Trait Anger Scale. The results showed substantial heritabilities for testosterone (approximately 60%) and moderate to fair heritabilities for the nine measures of the AHA syndrome (23–53%). The best fitting model for testosterone at two time points included a small age component and additive genetic and unique environmental factors, while a multivariate analysis of the nine AHA subscales resulted in an independent pathway model with two common additive genetic and two common unique environmental factors. No correlation between the common genetic factor influencing testosterone and the AHA subscales was found. We did, however, detect a negative correlation between the common environmental factor underlying testosterone and both common environmental factors influencing the nine AHA subscales, which may reflect a tendency for testosterone levels to rise and hostility to drop (or vice versa) after repeatedly experiencing success (or failure). Twin Research (2000) 3, 266–276.

We aimed to investigate the association between weight change from 20 years of age and insulin resistance (IR), and genetic and environmental relationships between these traits. In 594 Korean twins and family members (209 men, 385 women, 44.0 ± 10.8 years old), the percentage of weight change was calculated using self-reported body weight at 20 years of age and currently measured bodyweight. IR traits were assessed using fasting plasma glucose and insulin, the homeostasis model assessment of IR index (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI). Linear mixed analysis was applied after adjusting for household, body mass index (BMI) at the age of 20 years, age, sex, alcohol, smoking, physical activity, and caloric intake. Heritabilities and genetic and environmental correlations were estimated after adjusting for covariates. In 55 monozygotic twin pairs discordant for HOMA-IR level by >0.3, a conditional logistic regression analysis was conducted regarding weight change. Increases in glucose, insulin, and HOMA-IR and a decrease in QUICKI were associated with a higher percentage of weight change (p < .05). Estimated heritabilities for IR traits were 0.401–0.606 (p < .001). In cross-trait relationships, environmental correlations were -0.43–0.42 (p < .05 for all IR), while genetic correlations were -0.27–0.27 (p < .05 for QUICKI, insulin, and HOMA-IR). In 55 pairs of monozygotic twins, the odds ratio (95% confidence interval) for having a higher level of HOMA-IR was 1.10 (1.03–1.17) with 1% increase in weight change since 20 years old, after adjusting for lifestyle-related factors. In conclusion, both genetic and environmental influences played significant roles in the positive association between weight change from 20 years of age and IR.

The new West Japan Twins and Higher Order Multiple Births Registry was established by recruiting young twins and multiple births and by referrals from public health centers in the 1990s. The participants included in the survey comprised over 7800 twins and 4241 higher order multiples, and their families. Specifically, the present registry contains one of the largest triplet samples in the world. For these twins and multiples, data on year of delivery, mode of delivery, gestational age, intrapartum complications, longitudinal physical measures, motor milestones, cerebral palsy and feeding methods were obtained from records in the Maternal and Child Health Handbooks and schools. Participating mothers were asked to indicate family structure, parental educational history, maternal sleeping time, maternal health condition, maternal and paternal age at multiple delivery, complications during pregnancy, handedness of multiples and age at menarche of multiples. However, the zygosity differed among the various collaborating public health centers according to factors such as the time of investigation. Follow-up questionnaires have been mailed out every 3–4 years for longitudinal studies. This article describes the goals of this registry, recruitment of multiples and the focus of the study. The goals of this registry are not only to conduct research on human genetics and maternal and child health, but also to contribute to providing appropriate information for families with multiples.

Background: There continues to be significant investment in the detection of genotype × environment interaction (G × E) in psychiatric genetics. The implications of the method of assessment for the genetic analysis of psychiatric disorders are examined for simulated twin data on symptom scores and environmental covariates. Methods: Additive and independent genetic and environmental risks were simulated for 10,000 monozygotic (MZ) and 10,000 dizygotic (DZ) twin pairs and the ‘subjects’ administered typical simulated checklists of clinical symptoms and environmental factors. A variety of standard tests for G × E were applied to the simulated additive risk scores, sum scores derived from the checklists and transformed sum scores. Results: All analyses revealed no evidence for G × E for latent risk but marked evidence for G × E and other effects of modulation in the sum scores. These effects were all removed by transformation. An integrated genetic and psychometric model, accounting for both the causes of latent liability and a theory of measurement, was fitted to a sample of the simulated sum-score data and showed that there was no significant modulation of the parameters of the genetic model by environmental covariates (i.e., no G × E). Conclusions: Claims to detect G × E based on analytical methods that ignore the theory of measurement must be subjected to greater scrutiny prior to publication.

The aim of this study was to examine the effects of genetic and environment influences and sex on injury involvement using two sets of Finnish twin data. The younger participants were 955 twins born between 1983 and 1987, aged 20 to 24 years. The older participants were 12,428 twins born between 1930 and 1957, aged 33 to 60 years. Within-twin correlations in monozygotic and dizygotic twins suggested that genetic effects play no role in injury involvement among young twins, but do have some effect at older ages. The results indicated that environmental factors have greater importance in injury involvement than genetic factors in the younger twin data set (FT12), whereas in a middle-aged (33–60 years) twin data set, genetic effects explained about quarter of the variance in injury involvement. Sex was a strong contributing factor, with males being generally more prone to injuries than females.

Adiponectin has been associated with insulin resistance and type 2 diabetes mellitus and possibly fetal growth. Our aim was to assess the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and the birth sizes. We investigated four SNPs of ADIPOQ (rs182052, rs2241766, rs1501299, and rs266729) and birth height and weight in 237 healthy full-term neonates. The neonates with the rs182052 G allele had a greater birth weight (p = .043 in the dominant model) and a higher ponderal index (p = .028 in the additive model). The rs2241766 G allele was associated with a greater birth weight (p = .016 in the recessive model). In a logistic regression analysis, the homozygotes for the rs182052 G allele and those for the rs2241766 G allele showed a significant association with a greater birth weight above 90 percentile (OR 2.75, 95% CI 1.13–6.70 and OR 5.15, 95% CI 1.66–15.99, respectively). In conclusion, we found an association between rs182052 and rs2241766 and birth weight and ponderal index among healthy neonates and suggested that adiponectin might have some roles in fetal growth.

Twin registries have developed as a valuable resource for the study of many aspects of disease and society over the years in many different countries. A number of these registries include large numbers of twins with data collected at varying information levels for twin cohorts over the past several decades. More recent expansion of twin datasets has allowed for the collection of genetic data, together with many other levels of ‘omic’ information along with multiple demographic, physiological, health outcomes and other measures typically used in epidemiologic research. Other twin data sources outside these registries reflect research interests in particular aspects of disease or specific phenotypic assessment. Twin registries have the potential to play a key role in many aspects of the artificial intelligence/machine learning-driven projects of the future and will continue to keep adapting to the changing research landscape.

Twin–twin transfusion syndrome is the most common complication of monochorionic pregnancies affecting between 5 and 15% of such pregnancies and accounts for 15–77% of perinatal mortality in twins. The management of twin–twin transfusion syndrome is complex and various treatment modalities have been tried. This review critically evaluates the different management options available for the syndrome and recommends some guidelines for future interventional studies.

Accumulated evidence suggests that social support is influenced by genetic and environmental factors. However, there are little data that examine this issue from Asian samples. We reported results from a preliminary study that examined familial effects on social support in a Chinese adult twin sample. We administered a 10-item social support instrument that measures three dimensions of social support (i.e., objective support, subjective support, and utilization of support) developed for the Chinese population. Two hundred forty-two same-sex twin pairs, where both members of the pair completed the personal interview, were included in the final analysis. Structural equation modeling was used to estimate additive genetic (A), shared environmental (C), and nonshared environmental (E) effects on each dimension of social support. Familial factors (A+C) explained 56.63% [95% CI = 45.48–65.72%] and 42.42% [95% CI = 29.93–53.25%] of the total phenotypic variances of subjective support and utilization of support, respectively. For the objective support, genetic effects did not exist, but common environmental effect explained 37.56% [95% CI = 26.17–48.28%] of the total phenotypic variances. Neither gender nor age effects were seen on any dimension of social support. Except for objective support, genetic factors probably influence variation in subjective support and utilization of support. Shared environmental factors may influence all dimensions of social support.

Selective intrauterine growth restriction (sIUGR) in monochorionic twin pregnancies is associated with greater morbidity and mortality for both fetuses when compared to singleton and dichorionic pregnancies. This retrospective cohort study aimed to assess the perinatal outcomes of monochorionic twin pregnancies affected by this disorder and conducted expectantly, by analyzing the results according to the end-diastolic flow in the umbilical artery Doppler of the smaller twin (type I: persistently forward/type II: persistently absent or reversed/type III: intermittently absent or reversed). Seventy-five monochorionic diamniotic twin pregnancies with sIUGR were included in this study. sIUGR was defined by estimated fetal weight below the 3rd centile for gestational age, or below the 10th centile, when associated with at least one of the following three criteria: abdominal circumference below the 10th percentile, umbilical artery pulsatility index of the smaller twin above the 95th percentile, or estimated fetal weight discordance of 25% or more. Perinatal outcomes were analyzed from the prenatal period to hospital discharge and included perinatal death, neurological injury, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and sepsis. The mortality rate was 1.33% in this cohort. The overall morbidity rate was lower in type I twin pregnancies. In conclusion, this study shows that sIUGR type I has lower morbidity than types II and III in expectant management.

The Keio Twin Research Center (KoTReC) was established in 2009 at Keio University to combine two longitudinal cohort projects — the Keio Twin Study (KTS) for adolescence and adulthood and the Tokyo Twin Cohort Project (ToTCoP) for infancy and childhood. KoTReC also conducted a two-time panel study of self-control and psychopathology in twin adolescence in 2012 and 2013 and three independent anonymous cross-sectional twin surveys (ToTcross) before 2012 — the ToTCross, the Junior and Senior High School Survey and the High School Survey. This article introduces the recent research designs of KoTReC and its publications.

Chromosome 17q21.31 microdeletion syndrome is a genomic disorder caused by a recurrent 600 kb long deletion. The deletion affects the region of a common inversion present in about 20% of Europeans. The inversion is associated with the H2 haplotype carrying additional low-copy repeats susceptible to non-allelic homologous recombination, and this haplotype is prone to deletion. No instances of 17q21.31 deletions inherited from an affected parent have been reported, and the deletions always affected a parental chromosome with the H2 haplotype. The syndrome is characterized clinically by intellectual disability, hypotonia, friendly behavior and specific facial dysmorphism with long face, large tubular or pear-shaped nose and bulbous nasal tip. We present monozygotic twin sisters showing the typical clinical picture of the syndrome. The phenotype of the sisters was very similar, with a slightly more severe presentation in Twin B. The 17q21.31 microdeletion was confirmed in both patients but in neither of their parents. Potential copy number differences between the genomes of the twins were subsequently searched using high-resolution single nucleotide polymorphism (SNP) and comparative genome hybridisation (CGH) arrays. However, these analyses identified no additional aberrations or genomic differences that could potentially be responsible for the subtle phenotypic differences. These could possibly be related to the more severe perinatal history of Twin B, or to the variable expressivity of the disorder. In accord with the expectations, one of the parents (the mother) was shown to carry the H2 haplotype, and the maternal allele of chromosome 17q21.31 was missing in the twins.

We examined the item properties of the Two Peas Questionnaire (TPQ) among a sample of same-sex twin pairs from the Washington State Twin Registry. With the exception of the ‘two peas’ item, three of the mistakenness items showed differential item functioning. Results showed that the monozygotic (MZ) and dizygotic (DZ) pairs may differ in their responses on these items, even among those with similar latent traits of similarity and confusability. Upon comparing three classification methods to determine the zygosity of same-sex twins, the overall classification accuracy rate was over 90% using the unit-weighted pair zygosity sum score, providing an efficient and sufficiently accurate zygosity classification. Given the inherent nature of twin-pair similarity, the TPQ is more accurate in the identification of MZ than DZ pairs. We conclude that the TPQ is a generally accurate, but by no means infallible, method of determining zygosity in twins who have not been genotyped.

A new type of population-based database of multiples in childhood at the prefecture level was initiated in 2004 in Ishikawa Prefecture, Japan. We conducted an exhaustive search for demographic information concerning families with multiples, family support provided by governmental and medical institutions by mailed questionnaire, and at the same time tried to organize a human network to support such families. This registry aims not only to aid research on human genetics and maternal and child health, but also to contribute to the development of welfare programs for families with multiples.

Somatization is known to be more prevalent in Asian than in Western populations. Using a South Korean adolescent and young adult twin sample (N = 1754; 367 monozygotic male, 173 dizygotic male, 681 monozygotic female, 274 dizygotic female and 259 opposite-sex dizygotic twins), the present study aimed to estimate heritability of somatization and to determine common genetic and environmental influences on somatization and hwabyung (HB: anger syndrome). Twins completed self-report questionnaires of the HB symptoms scale and the somatization scale via a telephone interview. The results of the general sex-limitation model showed that 43% (95% CI [36, 50]) of the total variance of somatization was attributable to additive genetic factors, with the remaining variance, 57% (95% CI [50, 64]), being due to individual-specific environmental influences, including measurement error. These estimates were not significantly different between the two sexes. The phenotypic correlation between HB and somatization was .53 (p < .001). The bivariate model-fitting analyses revealed that the genetic correlation between the two symptoms was .68 (95% CI [.59, .77]), while the individual-specific environmental correlation, including correlated measurement error, was .41 (95% CI [.34, .48]). Of the additive genetic factors of 43% that influence somatization, approximately half (20%) were associated with those related to HB, with the remainder being due to genes unique to somatization. A substantial part (48%) of individual environmental variance in somatization was unrelated to HB; only 9% of the environmental variance was shared with HB. Our findings suggest that HB and somatization have shared genetic etiology, but environmental factors that precipitate the development of HB and somatization may be largely independent from each other.

Programme Committee: Elizabeth Bryan, Isaac Blickstein, Nick Martin, Pat Preedy, Tim Spector

Twins reared apart provide a fascinating experiment to distinguish genetic from environmental influences. However, there is as yet no broad report on distribution of twins reared apart, especially in the Chinese population. In this study, information on 18,295 volunteer twin pairs of all age groups was compiled in nine provinces or cities of China, and questionnaires were used for zygosity determination. It was discovered that twins reared apart from 0 to 10 years of age accounted for 2.2% of all twin interviewees, with the proportion of this 0–10 group separated before 1, 2, and 5 years old, accounting for 65.3%, 76.1%, and 91.3%, respectively. The proportion of twins reared apart is not significantly related to zygosity or gender, but it is related to region and twin age. As the age of twins lowers, the proportion of those reared apart gradually decreases. Twins reared apart will become rarer in the future and therefore should be cherished as a resource.

The purpose of Behavioral Genetics 5th edition (BG) is to cover the knowns and unknowns of behavior genetics, conveying the excitement of the field, its prospects, and something of the methods. Like the important American Psychologist (AP) paper ‘Intelligence: Knowns and Unknowns’ (Neisser et al., 1996), BG is designed to convey a consensus, in this case across fields as diverse as autism and xenophobia. Establishing and communicating this consensus is especially important for behavior genetics when many students are relatively unaware of the existence of biological differences. To meet this bold purpose the book needs to be accessible to those new to genetics while remaining accurate, and this goal is met admirably. The text is suffused with a calm and even handed approach that allows it to address its pedagogical task far better than most texts. It has been honed across the decades, including a complete rewrite (3rd edition), and, now, two rounds of fine-tuning. This polish pays off: the book reads very well, is well indexed, and integrated.

Objective: To investigate the occurrence of early-onset neonatal sepsis (EOS) in twin–twin transfusion syndrome (TTTS) managed with laser surgery.

Study design: We performed a prospective cohort study of all consecutive TTTS cases treated with laser surgery (TTTS group) delivered at the Leiden University Medical Center. We recorded the occurrence of EOS, defined as a positive blood culture ≤72 hours postpartum (proven sepsis) or administration of a full course of antibiotics due to risk factors or signs of sepsis, in the absence of a positive blood culture (suspected sepsis). Perinatal variables in the TTTS group were compared with uncomplicated monochorionic twins (no-TTTS group). A multivariate model was generated, examining the association between EOS and gestational age at birth, interval between laser surgery and birth, anterior placenta, laser period (first study period: 2002–2008; second study period: 2009–2015), and preterm premature rupture of membranes (PPROM).

Results: The rates of combined suspected and proven EOS in the TTTS group and no-TTTS group were 16% (68/416) and 10% (55/542), respectively (relative ratio [RR] 1.74, 95% confidence interval [CI] 1.19–2.55). Multivariate analysis showed that EOS in the TTTS group was independently associated with lower gestational age at birth (odds ratio [OR] 0.75, 95% CI 0.63–0.88), first study period (OR 2.25, 95% CI 1.08–4.67) and PPROM (OR 2.47, 95% CI 1.28–4.75).

Conclusion: The rate of EOS in the TTTS group is low, but increased compared to the no-TTTS group. EOS in TTTS is independently associated with premature delivery, earlier laser period, and PPROM.

Several epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake — indicating glucose intolerance and insulin resistance — among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.