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.

The genetic and environmental contributions of negative valence systems (NVS) to internalizing pathways study (also referred to as the Adolescent and Young Adult Twin Study) was designed to examine varying constructs of the NVS as they relate to the development of internalizing disorders from a genetically informed perspective. The goal of this study was to evaluate genetic and environmental contributions to potential psychiatric endophenotypes that contribute to internalizing psychopathology by studying adolescent and young adult twins longitudinally over a 2-year period. This report details the sample characteristics, study design, and methodology of this study. The first wave of data collection (i.e., time 1) is complete; the 2-year follow-up (i.e., time 2) is currently underway. A total of 430 twin pairs (N = 860 individual twins; 166 monozygotic pairs; 57.2% female) and 422 parents or legal guardians participated at time 1. Twin participants completed self-report surveys and participated in experimental paradigms to assess processes within the NVS. Additionally, parents completed surveys to report on themselves and their twin children. Findings from this study will help clarify the genetic and environmental influences of the NVS and their association with internalizing risk. The goal of this line of research is to develop methods for early internalizing disorder risk detection.

Until now, data have not been available to elucidate the genetic and environmental sources of comorbidity between all 10 DSM-IV personality disorders (PDs) and cocaine use. Our aim was to determine which PD traits are linked phenotypically and genetically to cocaine use. Cross-sectional data were obtained in a face-to-face interview between 1999 and 2004. Subjects were 1,419 twins (µage = 28.2 years, range = 19–36) from the Norwegian Institute of Public Health Twin Panel, with complete lifetime cocaine use and criteria for all 10 DSM-IV PDs. Stepwise multiple and Least Absolute Shrinkage and Selection Operator (LASSO) regressions were used to identify PDs related to cocaine use. Twin models were fitted to estimate genetic and environmental associations between the PD traits and cocaine use. In the multiple regression, antisocial (OR = 4.24, 95% CI [2.66, 6.86]) and borderline (OR = 2.19, 95% CI [1.35, 3.57]) PD traits were significant predictors of cocaine use. In the LASSO regression, antisocial, borderline, and histrionic were significant predictors of cocaine use. Antisocial and borderline PD traits each explained 72% and 25% of the total genetic risks in cocaine use, respectively. Genetic risks in histrionic PD were not significantly related to cocaine use. Importantly, after removing criteria referencing substance use, antisocial PD explained 65% of the total genetic variance in cocaine use, whereas borderline explained only 4%. Among PD traits, antisocial is the strongest correlate of cocaine use, for which the association is driven largely by common genetic risks.

Children and adolescents who are victims or perpetrators of bullying victimization are at elevated risk for maladjustment problems, concurrently and in the long run. Previous studies suggest that this correlation is partly explained by genetic influence. However, whether the genetic correlation is independent of a causal effect of victimization on maladjustment remains unclear. Using data from 2,510 females from the TwinsUK registry, we applied an innovative extension of the Cholesky decomposition to investigate to what extent the association between victimization in adolescence and self-reported depressive episodes in adulthood is caused by shared genetic effects (pleiotropy), and to what extent it is due to a phenotypic causal relationship. We find that around 60% of the association between victimization and self-reported depressive episodes is due to a causal effect of victimization on depressive episodes, and 40% is due to pleiotropic effects. These findings underline the importance of integrating genetic information into social science research and demonstrate a neat strategy to elucidate causal mechanisms in the absence of experimental designs.

A discordant twin gestation, in which one fetus is significantly growth restricted, compared to the other normal twin, is a unique model that can be used to elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. In many model systems, placental transcription factor genes regulate fetal growth. Transcription factors regulate growth through their activation or repression of downstream target genes that mediate important cell functions. The objective of this study was to determine the expression of the placental HLX homeobox gene transcription factor and its downstream target genes in dizygotic twins with growth discordance. In this cross-sectional study, HLX and its downstream target genes’ retinoblastoma 1 (RB1) and cyclin kinase D (CDKN1C) expression levels were determined in placentae obtained from dichorionic diamniotic twin pregnancies (n = 23) where one of the twins was growth restricted. Fetal growth restriction (FGR) was defined as small for gestational age with abnormal umbilical artery Doppler indices when compared with the normal control co-twin. Homeobox gene HLX expression was significantly decreased at both the mRNA and protein levels in FGR twin placentae compared with the normal control co-twin placentae (p < .05). Downstream target genes CDKN1C and RB1 were also significantly decreased and increased, respectively, at both the mRNA and protein levels in FGR twin placentae compared with normal control co-twin placentae (p < .05). Together, these observations suggest an important association between HLX transcription factor expression and abnormal human placental development in discordant twin pregnancies.

Monozygotic (MZ) and dizygotic (DZ) twins participate in research that partitions variance in health, disease, and behavior into genetic and environmental components. However, there are other innovative roles for twins in medical research. One such way is involving MZ and/or DZ twins in co-twin control-designed randomized controlled trials (RCTs). To our knowledge, no reviews have been conducted that summarizes the involvement of twins in RCTs. Therefore, we conducted a systematic literature search using the U.S. Clinical Trials Database, NHS electronic databases, MEDLINE, EMBASE, and PsychINFO for RCTs on publications involving MZ and/or DZ twins as RCT participants. Out of the 186,027 clinical trials registered in the U.S. clinical trial register ClinicaTrails.gov, only six RCTs used twins as participants. From 1,598 articles identified in our search, 50 peer-reviewed English language publications met our pre-defined inclusion criteria. Sample sizes for RCTs have ranged from a total number of participants from 2 to 1,162; however, 32 (64%) studies had a sample size of 100 or less, and of those, 12 (24%) had fewer than 10. Both MZ and DZ twins have been recruited to the RCTs. In most instances (33/50) each twin from a pair were assigned to different study arms. Most of those studies included MZ twins only. Despite the methodological advantages, the use of MZ and DZ twins as participants in interventional RCTs appeared limited. The continuous development of innovative twin designs, especially RCTs, indicates that twin research can extend beyond the more widely recognized heritability estimates.

In the 19th century, a series of international statistical congresses began that were important for population studies, including twin research. The introduction of common rules for the national demographic registers enabled scientists to contribute to the genesis of statistical research. The congress in St. Petersburg in 1872, in particular, focused on the movements of the population, and how they should be registered. Among the facts to be recorded were in multiple births, the sex and number of children born alive or still-born, whether legitimate or illegitimate, and the age of the mother at the date of the births. During the history of twin research, Hellin's law has played a central role because it is an approximately correct association between the rates of multiple maternities. It has been mathematically proven that Hellin's law does not hold as a general rule. Analyses show divergences from the law that are difficult to explain and/or eliminate. Varying improvements of this law have been proposed. The majority of all studies of Hellin's law are based on empirical rates of multiple maternities, ignoring random errors. Such studies can never confirm the law, but only identify errors with respect to Hellin's law that are too large to be characterized as random. It is of particular interest to note and explain why the rates of higher multiple maternities are sometimes too high or too low when Hellin's law is used as a benchmark. Studies have shown that there were investigators before Hellin who have contributed substantially to Hellin's law. In this article, we re-examine some old data sets and contributions in which Hellin's law has been evaluated and also analyze recent data.

Highlights from the 16th International Twin Congress, held in Madrid, Spain from November 16–18, 2017, are presented. The Twin Congress, formerly held every three years, now takes place biennially with a single-day meeting organized during the off years. This meeting is the largest gathering of scientific twin researchers, medical personnel, and representatives of multiple birth organizations in the world. This overview is followed by reviews of recent twin research and commentary concerning partner aggression, ABO incompatibility in dizygotic twins, growth discordance in a monoamniotic twin pair and twin implantation. The article closes with summaries of timely topics in the media, namely a father's finding of his long-lost twin children, early results from the NASA twin experiment, twin brothers at the center of the October 2017 Las Vegas attack, retired twin airline pilots, and clips from recent films with twin-based themes.