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.

Dr H. Keith Sigmundson co-authored a seminal article (with the late Dr Milton Diamond) that revealed the truth about a highly controversial twin case. Specifically, the genitals of an infant male monozygotic twin were accidentally destroyed during a medical procedure performed to alleviate his difficult urination. The child’s parents were advised to physically and psychologically transform their twin son into a girl. Occasional reports about the case indicated that the plan was successful, but some members of the medical community were doubtful. An interview with Dr H. Keith Sigmundson, for the purpose of obtaining his unique perspective on this case, is presented. The interview is followed by a tribute to our late twin research colleague, Dr John L. Hopper, of Melbourne, Australia. A review of research on nonhuman primate twinning, an overview of a 2024 documentary film, The Accidental Twins, and a story of different looking identical twin newborns are also provided.

The objective of this study was to investigate the genetic link between the age at first birth (AFB) and the occurrence of preterm labor and delivery, utilizing Mendelian randomization (MR) data alongside genomewide association analysis (GWAS). We obtained AFB-related GWAS summary data from the European Bioinformatics Institute database and preterm labor and delivery data was sourced from the FinnGen Consortium. The study considered AFB as exposure variables, with the incidence of preterm labor and delivery serving as the outcome variable. Several MR analysis methods, such as inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted mode were utilized. Besides MR-Egger intercepts, Cochrane’s Q test evaluated heterogeneity in the MR data, while MR-PRESSO test checked for horizontal pleiotropy. To assess the association’s sensitivity, A leave-one-out approach was utilized to evaluate the sensitivity of the association. The IVW analysis validated that AFB is an independent risk factor for preterm labor and delivery (p < .001). Horizontal pleiotropy was unlikely to bias causality (p > .05). The likelihood of horizontal pleiotropy affecting causality was low (p > .05), and there was no indication of heterogeneity among the genetic variants (p > .05). Ultimately, a leave-one-out analysis confirmed the stability and reliability of this correlation. Our research indicated that AFB is a protective factor for preterm labor and delivery. Further research is required to clarify the possible mechanisms.

We analyzed whole-genome sequencing (WGS) data from 51 populations and combined WGS and array data from 89 populations. Multiple types of polygenic scores (PGS) were employed, derived from multi-ancestry, between-family genome-wide association study (GWAS; MIX-Height), European-ancestry, between-family GWAS (EUR-Height), and European-ancestry siblings GWAS (SIB-Height). Our findings demonstrate that both genetic and environmental factors significantly influence adult body height between populations. Models that included both genetic and environmental predictors best explained population differences in adult body height, with the MIX-Height PGS and environmental factors (Human Development Index [HDI] + per capita caloric intake) achieving an R2 of .83. Our findings shed light on Deaton’s ‘African paradox’, which noted the relatively tall stature of African populations despite poor nutrition and childhood health. Contrary to Deaton’s hypotheses, we demonstrate that both genetic differences and environmental factors significantly influence body height in countries with high infant mortality rates. This suggests that the observed tall stature in African populations can be attributed, in part, to a high genetic predisposition for body height. Furthermore, tests of divergent selection based on the QST (i.e., standardized measure of the genetic differentiation of a quantitative trait among populations) and FST (neutral marker loci) measures exceeded neutral expectations, reaching statistical significance (p < .01) with the MIX-Height PGS but not with the SIB-Height PGS. This result indicates potential selective pressures on body height-related genetic variants across 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.

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.

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.