Substance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis. We also additionally describe two longitudinal cohorts — the Brisbane Longitudinal Twin Study in Australia and the Lifelines Cohort Study in the Netherlands. By applying the methodological framework to these two unique datasets, our future research will explore the complex interplay between genetic factors, gene expression, and environmental influences on substance use behaviors and disorders across different life stages and populations.

We evaluated the prevalence and risk factors for child maltreatment in multiples aged 3 years and compared them to singletons in Japanese population-based data. Records on child maltreatment and health check-ups at 3 years of age from 17,125 singletons, 488 twins and 18 triplets were collected from a Public Health Center between April 2007 and March 2011. The associations of child maltreatment with potential risk factors were analyzed using the logistic regression model. Out of all children, 76 (4.31 per 1000) children had documented maltreatment including 69 (4.03 per 1000) singletons and seven (14.31 per 1000) twins. All of the cases in twins were physical abuse (100%) and nearly half of the cases (43%) included emotional abuse. Among twins, 86% of the biological mothers were suspected. The alleged perpetrators of twins showed a significantly higher rate of maternal depression compared to those of singletons. After adjusting the results for a number of potential biological and social risk factors, twins or triplets had a higher risk for maltreatment than singletons (OR 3.39, 95% CI [1.17, 9.83]). Healthcare providers should be aware that a multiple birth can place considerable stress on a family leading to child maltreatment and should provide appropriate support and intervention for mothers with multiples.

Studies concerning twins with a sociological focus are scarce in Hungary as well as international research, although the number of twin births has increased dramatically worldwide. The raising and education of twins are tasks demanding special attention from both the family and institutions. In our study we examine these aspects, looking back from adulthood, using the narrow scope of the available data from research based on the ‘Hungarostudy 2021’ database (N total: 7000; n twins: 106). Our results, corresponding to the hypotheses of educational sociology, demonstrate how the relationships between family size and school career and increasing number of siblings reduces the chances of high educational attainment. A regression analysis confirmed that both the number of siblings and a later position in the birth order reduces the chance of obtaining a higher education. For the second child in a family, the chance of earning a university degree is reduced to to 0.743. The role of a large family concerning higher education showed a stronger relationship in the case of twins compared to nontwins. For twins, the sibling pattern has a decisive effect in educational attainment. Twins themselves have a 1.449 times higher chance of obtaining a higher education compared to nontwins (p = 0.101), and fraternal twins have half (0.517) the chance of obtaining a higher education compared to identical twins; but both results are not significant (p = 0.156).

Placental vascular anastomoses are traditionally thought to exist exclusively in monochorionic pregnancies. However, they have been reported in dichorionic twin pregnancies as well. In turn, twin to twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) have also been noted to impact some of these gestations. Through discussion of one such case at our institution along with a review of the available literature, we review the proposed pathophysiology of placental vascular anastamoses in dichorionic twin gestations, and aim to raise awareness of the possibility of associated pathologies in dichorionic gestations. This is an emerging area of literature that will require future study to guide prenatal surveillance and mitigate morbidity.

This study examines the changes over time of the twinning rate and infant and child mortality across 17 rural villages in the province of Zaragoza (Spain) over a span of 200 years. The aim is to understand how the twinning rate evolved in conjunction with the processes of economic and social modernization, as well as the demographic transition. During the period analyzed, the twinning rate increased by 10%, rising from 1.26 per 1000 births in the second half of the 18th century to 1.38 per 1000 births in the first half of the 20th century. This rate varied due to hereditary issues, biological factors such as the mother’s age and parity, and socioeconomic features like family occupation and the mother’s education level. In terms of child mortality, twins historically faced a significantly higher mortality rate. However, they benefited greatly from the mortality transition, at least in absolute numbers. While nearly 60% of twins did not survive beyond 5 years of age in earlier periods, the mortality rate for twins decreased to 40% by the first half of the 20th century. The excess mortality was particularly severe for girls, driven by a widespread preference for sons, which led to higher mortality rates for girls in the first 5 years of life, especially in the earliest months. These findings help us understand the improvements in uterine and childhood survival rates for contemporary twins, which can be attributed to the socioeconomic and medical advancements of the 20th century.

Although the relationship between gaming addiction (GA) and attention deficit hyperactivity disorder (ADHD) is well established, the causal mechanism of this relationship remains ambiguous. We aimed to investigate whether common genetic and/or environmental factors explain the GA-ADHD relationship. We recruited 1413 South Korean adult twins (837 monozygotic [MZ], 326 same-sex dizygotic [DZ], and 250 opposite-sex DZ twins; mean age = 23.1 ± 2.8 years) who completed an online survey on GA and related traits. Correlational analysis and bivariate model-fitting analysis were conducted. Phenotypic correlation between GA and ADHD in the present sample was 0.55 (95% CI [0.51, 0.59]). Bivariate model-fitting analysis revealed that genetic variances were 69% (95% CI [64%, 73%]) and 68% (95% CI [63%, 72%]) for ADHD and GA respectively. The remaining variances (ADHD: 31%; GA: 32%) were associated with nonshared environmental variances, including measurement error. Genetic and nonshared environmental correlations between ADHD and GA were 0.68 (95% CI [0.62, 0.74]) and 0.22 (95% CI [0.13, 0.30]) respectively, which indicates that shared genes can explain 82% of the phenotypic correlation between ADHD and GA. Our study demonstrated that the ADHD-GA association was largely due to shared genetic vulnerability.

Twins lag behind singletons in their early psychomotor development, but little is known about how chorionicity affects this difference. We compared early psychomotor development in singletons, monochorionic (MC) twins and dichorionic (DC) twins. Our longitudinal data from the Japan Environment and Children’s Study (JECS; see Appendix) included 98,042 singletons, 577 MC twins and 1051 DC twins representing the general Japanese population. Chorionicity was evaluated by ultrasound images and complemented by postnatal pathological examinations. Five domains of psychomotor development were evaluated at 6 time points from 6 months to 3 years of age using the Ages and Stages Questionnaires (ASQ-3). The data were analyzed using linear regression models. Twins lagged behind singletons in all areas of psychomotor development during infancy. This gap decreased over time but was still noticeable at 3 years of age. More than half of this difference was attributed to twins having lower birth weight and being born earlier in gestation. MC twins showed slightly delayed development compared to DC twins, but this difference was minor compared to the overall gap between twins and singletons. Twins delay singletons in their early psychomotor development, and this delay is not specific to MC twinning.

We investigated whether an observed reduction in overall childhood cancer risk (<15 years of age) in twins has been sustained, and how this extends into young adulthood. We searched for English language publications reporting childhood cancer risk in twins, obtained unpublished data directly from some authors, and updated a meta-analysis. We used the Swedish Multigeneration Register to investigate the age to which the reduced overall risk of childhood cancer (observed previously using that Swedish dataset and in this and earlier meta-analyses) persisted into the teenage/young adult years, and which specific tumors accounted for the overall risk reduction beyond childhood. Our meta-analysis of studies of aggregate childhood cancer risk in twins confirmed their approximate 15% reduction in cancer mortality and incidence. Further analysis of Swedish Multigeneration Register data for 1958 to 2002 suggested these reduced risks of cancer (particularly leukaemias and renal tumors) extended from childhood to young adult ages. Reduced risks of these and some other specific tumor types occurring across childhood/teenage/young adult years appeared to account for most of the overall risk reduction. Our results suggest a persistent reduction of overall childhood cancer risk in twins and that this extends into young adulthood. Risk reductions for several specific tumors might account for this and, although there are several potential explanations, intrauterine growth patterns of twins might be a major contributor.

As with many other musical traits, the social environment is a key influence on the development of singing ability. While the familial singing environment is likely to be formative, its role relative to other environmental influences such as training is unclear. We used structural equation modeling to test relationships among demographic characteristics, familial environmental variables (early and current singing with family), vocal training, and singing ability in a large, previously documented sample of Australian twins (N = 1163). Notably, early singing with family, and to a lesser extent vocal training, predicted singing ability, whereas current singing with family did not. Early familial singing also mediated the relationship between sex and singing ability, with men who sang less with family during childhood showing poorer ability. Bivariate twin models between early familial singing and singing ability showed the phenotypic correlation was largely explained by shared environmental influences. This raises the possibility of a sensitive period for singing ability, with sociocultural expectations around singing potentially differentiating the developmental trajectories of this skill for men and women.

Social support is often considered an environmental factor affecting health, especially in aging populations. However, its genetic underpinnings suggest a more complex origin. This study investigates the heritability of social support through applying a threshold model on data of a large adult sample of twins (N = 8019) from the Netherlands Twin Register, collected between 2009 and 2011. The study employed the Duke – UNC Functional Social Support Questionnaire to assess social support quality. Our analysis revealed genetic contributions to social support, with heritability estimated at 37%, without a contribution of shared environment and no differences between men and women in heritability. The study’s results underscore the complexity of social support as a trait influenced by genetic and environmental factors, challenging the notion that it is solely an environmental construct.

Although there is evidence that social status has a genetic basis, it is less known whether the genetic predisposition differs between men and women as well as among different status indicators and whether there are any intercorrelations among predispositions of status indicators. We therefore investigated the genetic predisposition for different indicators of social status separately for men and women, using polygenic scores obtained from the Wisconsin Longitudinal Study. We used multivariate polygenic regression of 7 different social status indicators on a total of 24 different polygenic scores. We find that in both men and women, wages and education show more associations with polygenic scores than the other status indicators. Also, the genetic predispositions for education and wages are correlated in both men and women, whereas in men more than in women, the genetic predispositions seem to cluster into wages and education on the one hand, and status indicators of position in the hierarchy, on the other hand, with being in a management position somewhere in between. These findings are consistent with an assumption of two different forms of selection pressure associated with either cognitive skill or dominance, which holds true particularly in men. We conclude that the genetic predisposition to higher social status may have changed even though the importance of the cultural trait of social status may have been very constant. Social status may thus be an example of a social trait of constant importance, but with a changing genetic predisposition.

Previous studies have shown that mothers of naturally conceived dizygotic (DZ) twins tend to be taller, older, and smoke more than mothers of naturally conceived monozygotic (MZ) twin and mothers of singletons. Here, we investigate whether mothers of naturally conceived DZ twins differ from mothers who conceived their DZ twins after medically assisted reproduction (MAR) in eight maternal traits related to fertility based on observational survey data. We include data from 33,648 mothers from the Netherlands Twin Register (NTR) and 1660 mothers of twins from the Norwegian Mother, Father and Child Cohort Study (MoBA). We contrast mothers of naturally conceived DZ twins with mothers of MAR DZ twins. Next, we further segment the MAR group into mothers who underwent hormonal induction of ovulation but not in vitro fertilization (IVF) and those who IVF twins, comparing them both to each other and against the mothers of naturally conceived DZ twins. Mothers of naturally conceived DZ twins smoke more often, differ in body composition, have a higher maternal age and have more offspring before the twins than mothers of MZ twins. Compared to MAR DZ twin mothers, mothers of naturally conceived DZ twins have fewer miscarriages, lower maternal age and increased height, more offspring and are more often smokers. BMI before the twin pregnancy is similar in both natural and MAR DZ twin mothers. Mothers who received hormonal induction of ovulation (OI) have a lower maternal age, fewer miscarriages, and a higher number of offspring before their twin pregnancy than twin mothers who received IVF and/or intracytoplasmic sperm injection (ICSI) treatments. Our study shows that twin mothers are a heterogenous group and the differences between twin mothers should be taken into account in epidemiological and genetic research that includes twins.

Between 2006 and 2021, the Hungarian Twin Registry (HTR) operated a volunteer twin registry of all age groups (50% monozygotic [MZ], 50% dizygotic [DZ], 70% female, average age 34 ± 22 years), including 1044 twin pairs, 24 triplets and one quadruplet set. In 2021, the HTR transformed from a volunteer registry into a population-based one, and it was established in the Medical Imaging Centre of Semmelweis University in Budapest. Semmelweis University’s innovation fund supported the development of information technology, a phone bank and voicemail infrastructure, administrative materials, and a new website was established where twins and their relatives (parent, foster parent or caregiver) can register. The HTR’s biobank was also established: 157,751 individuals with a likely twin-sibling living in Hungary (77,042 twins, 1194 triplets, 20 quadruplets, and one quintuplet) were contacted between February and March of 2021 via sealed letters. Until November 20, 2022, 12,001 twin individuals and their parents or guardians (6724 adult twins, 3009 parents/guardians and 5277 minor twins) registered, mostly online. Based on simple self-reports, 37.6% of the registered adults were MZ twins and 56.8% were DZ; 1.12% were triplets and 4.5% were unidentified. Of the registered children, 22.3% were MZ, 72.7% were DZ, 1.93% were triplets, and 3.05% were unidentified. Of the registered twins, 59.9% were female (including both the adult and minor twins). The registration questionnaire consists of eight parts, including socio-demographic and anthropometric data, smoking habits and medical questions (diseases, operations, therapies). Hungary’s twin registry has become the sole and largest population-based twin registry in Central Eastern Europe. This new resource will facilitate performing world-class modern genetic research.

Researchers have proposed that culture significantly influences perceived stress (PS). To date, however, twin studies on PS have been conducted mostly in western, individualistic cultures, which demonstrate that PS due to controllable (personal) life events is more heritable than PS due to uncontrollable (network) life events. This study aimed to investigate genetic and environmental influences on PS in South Korean twins. South Korea practices a dominant collectivist culture. In total, 1372 twin individuals (mean age = 22.4 ± 2.5 years) completed an online survey on PS, which consisted of the scales, Friendship, Academic Stress, Future Career, Family Conflicts, and Family Financial Difficulties (FFD). Friendship, Academic Stress, and Future Career can be considered PS due to personal life events, and Family Conflict and FFD, PS due to network life events. The general sex-limitation model-fitting analysis revealed the absence of qualitative or quantitative sex differences in genetic and environmental influences. Specifically, additive genetic influences were predominant for Friendship (63%), Academic Stress (67%), and Future Career (57%) for both sexes, with the remaining variance attributable to nonshared environmental influences. In contrast, shared environmental influences were largest for Family Conflict (47% for both genders) and FFD (64% for males, 63% for females) with no significant genetic effects. Despite known cultural differences in the means and variances of PS, South Korean twins exhibited significant genetic effects in PS due to personal life events and large shared environmental effects in PS due to network life events, which is similar to western samples.

TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country’s population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database that will allow the study of complex traits in the Mexican population, valuable not only for our consortium, but also for the worldwide scientific community, by providing new insights of understudied genetically admixed populations.

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.

Fetuses undergo major surgical stress as well as fluid shifts secondary to both twin-twin transfusion (TTTS) as well as the fetoscopic surgery for treatment of TTTS. While the pathophysiology of TTTS is understood, the acute metabolic changes that fetuses experience from fetoscopic surgery are not. We sought to evaluate the changes in recipient metabolomic profile secondary to TTTS surgery. Amniotic fluid was collected at the beginning and end of four TTTS surgical cases performed from 12/2022−2/2023. Samples were immediately processed and evaluated via NMR-based Metabolomics Facility protocol. In univariate analysis, 12 metabolites (glucose, lactate, and 10 key amino acids) showed statistically significant changes between the beginning and end of the surgery. Among these, 11 metabolites decreased at the end, while only lactate increased. Supervised oPLS-DA modeling revealed pyruvate and lactate as the two metabolites most impact on the variance between cases, and that 40% of metabolomic changes could be attributed directly to the timing that the sample was taken (i.e., if pre- or postoperatively). These results indicate significant metabolic changes in the recipient twin during fetoscopic surgery for TTTS. These findings of decreased glucose, increased lactate, and decreased amnio acids would indicate increased catabolism during surgery. This study raises questions regarding optimal maternal and fetal nutrition during surgery and if nutritional status could be optimized to further improve twin survival during fetoscopic surgery.

This Position Statement provides guidelines for health professionals who work with individuals and families seeking predictive genetic testing and laboratory staff conducting the tests. It presents the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity, and adults living with reduced or fluctuating cognitive capacity.

Predictive Testing Recommendations: (1) Predictive testing in adults, young people and children should only be offered with pretest genetic counseling, and the option of post-test genetic counseling. (2) An individual considering whether to have a predictive test should be supported to make an autonomous and informed decision. Regarding Children and Young People: (1) Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies, or other medical interventions in the immediate future. (2) Where symptoms are likely to develop in childhood, in the absence of direct medical benefit from this knowledge, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. (3) Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make an autonomous and informed decision. This is applicable regardless of whether there is some action that can be taken in adulthood.

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.

There are sex-dependent differences in hematological and biochemical variables in adulthood attributed to the predominant effects of testosterone in males and estrogen in females. The Twin Testosterone Transfer (TTT) hypothesis proposes that opposite-sex females may develop male-typical traits due to exposure to relatively higher levels of prenatal testosterone than same-sex females. Additionally, prenatal testosterone exposure has been suggested as a correlate of current circulating testosterone levels. Consequently, opposite-sex females might exhibit male-typical patterns in their hematological and biochemical variables. Despite this hypothesis, routine laboratory investigations assign the same reference range to all females. Our cross-sectional study, conducted in Tamale from January to September 2022, included 40 twins, comprising 10 opposite-sex (OS) males (25%), 10 OS females (25%), and 20 same-sex (SS) females (50%), all aged between 18 and 27 years. Fasting venous blood samples were collected and analyzed using automated hematology and biochemistry laboratory analyzers. Results indicated that levels of hemoglobin, serum creatinine, gamma-glutamyl transferase, total protein, globulins, and total testosterone were significantly higher in OS males than OS females. Conversely, total cholesterol and low-density lipoprotein cholesterol were significantly higher in OS females than OS males. Unexpectedly, levels of low-density lipoprotein cholesterol and total testosterone were significantly higher in SS females than OS females. Contrary to expectations, opposite-sex females did not exhibit male-typical patterns in their hematological and biochemical variables. This suggests that the TTT effect may not occur or may not be strong enough to markedly affect hematological and biochemical variables in OS females.