The 4th International Network of Twin Registries (INTR) Consortium Meeting took place in Osaka, Japan, September 28–29, 2015. The venue was the Osaka Medical Center for Medical Innovation and Translational Research. An overview of presentations and other activities is provided. Next, 1930s research on familial fraternal twinning, preference for masculine faces, physical aggression and epigenetics, and a prenatal education program for parents of multiples are described. Current twin-related events include the 2016 Guinness Book of World Records (GWR), the oldest living male twins, newly reunited twins, the birth of panda twins and a controversial twin-based website.

Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).

In our three-stage questionnaire study we investigated patterns of twin and familial aggregation of osteoarthritis (OA) for commonly affected joints. The baseline questionnaire study of the Finnish Twin Cohort was performed in 1975. In 1990, 4095 twin pairs of the same gender born 1930–1957 responded to a questionnaire and reported whether they had OA diagnosed by a physician. In 1996 both twins of 266 pairs of which at least one had reported OA in 1990 responded to a detailed questionnaire on joint-specific OA, including family history of OA. In male pairs shared (non-genetic) familial effects accounted for 37% of the total variance in liability to OA and unshared environmental effects for 63%. In female pairs additive gene effects explained 44% of the variance in liability to OA, and unshared environmental effects for 36%. Familial aggregation of finger and knee OA was clearly higher than that of hip OA. Twin-pair discordance for OA was, to some extent, associated with body-mass index, occupational loading and trauma. Our results indicate that genetic effects may be modulated by sex or by environmental factors distributed differently between men and women. Based on our joint-specific data finger and knee joints are the most optimal targets for studies of genetic factors predisposing to the development of OA.

Aretrospective study involving 623 twin and 1246 singleton births was conducted to compare the two groups with regard to selected maternal, fetal and labor and delivery characteristics and outcomes. Maternal age and parity were significantly higher for twins. The risks of preterm delivery, arrival in the labor ward in second stage of labor, cesarean births and postpartum haemorrhage were significantly higher in twin than in singleton births. In vaginal deliveries twin mothers were significantly less likely to have had episiotomies or perineal lacerations. There was no difference in the duration of the third stage of labor or in the incidence of retained placentae. Antepartum haemorrhage was a less likely indication for cesarean delivery among twins, while there was no significant difference in the likelihood of severe pre-eclampsia/eclampsia being an indication. Singleton babies were significantly heavier than twins. The incidences of malpresentation, low birth weight, stillbirths and of admission of live births to the neonatal intensive care unit were significantly higher in twins. There was no difference in the rate of instrumental vaginal delivery, or in the route of delivery of fetuses presenting by the breech. There is the need for detailed study of the incidences of antepartum haemorrhage and hypertensive diseases in twin and singleton pregnancies and of the factors determining the mode of delivery when such complications arise. Labor and delivery should also be examined to determine any differences between the two groups, especially in the first and second stages.

Fellman and Eriksson (2010) cited my suggestion that the sex ratio (proportion male) of monozygotic (MZ) twins is lower than that of dizygotic (DZ) twins (James 1975). Here I offer elaborations on and potential explanations for this.

Twins can help researchers disentangle the roles of genes from those of the environment on human traits, health, and diseases. To realize this potential, the Australian Twin Registry (ATR), University of Melbourne, and the Charles Perkins Centre (CPC), University of Sydney, established a collaboration to form the Twins Research Node, a highly interconnected research facility dedicated specifically to research involving twins. This collaboration aims to foster the adoption of twin designs as important tools for research in a range of health-related domains. The CPC hosted their Twins Research Node's launch seminar entitled ‘Double the power of your research with twin studies’, in which experienced twin researchers described how twin studies are supporting scientific discoveries and careers. The launch also featured twin pairs who have actively participated in research through the ATR. Researchers at the CPC were surveyed before the event to gauge their level of understanding and interest in utilizing twin research. This article describes the new Twins Research Node, discusses the survey's main results and reports on the launch seminar.

Life-course experiences have been postulated to program hypothalamus–pituitary–adrenal (HPA) axis activity, suggesting that HPA axis activity is, at least partially, stable over time. Yet, there is paucity of data on the long-term stability of cortisol production and metabolism. We performed a prospective follow-up study in twins recruited from a nationwide register to estimate the stability of cortisol production and metabolism over time, and the contribution of genetic and environmental factors to this stability. In total, 218 healthy mono- and dizygotic twins were included. At the ages of 9, 12 and 17 years, morning urine samples were collected for assessment (by gas chromatography-tandem mass spectrometry) of cortisol metabolites, enabling the calculation of cortisol metabolite excretion rate and cortisol metabolism activity. Our results showed a low stability for both cortisol metabolite excretion rate (with correlations <.20) and cortisol metabolism activity indices (with correlations of .25 to .46 between 9 and 12 years, −.02 to .15 between 12 and 17 years and .09 to .28 between 9 and 17 years). Because of the low stability over time, genetic and environmental contributions to this stability were difficult to assess, although it seemed to be mostly determined by genetic factors. The low stability in both cortisol production and metabolism between ages 9 and 17 years reflects the dynamic nature of the HPA axis.

Numerous papers have investigated the distribution of birth weight. This interest arises from the association between birth weight and the future health condition of the child. Birth weight distribution commonly differs slightly from the Gaussian distribution. The distribution is typically split into two components: a predominant Gaussian distribution and an unspecified ‘residual’ distribution. In this study, we consider birth weight data from the Åland Islands (Finland) for the period 1885–1998. We compare birth weight between males and females and among singletons and twins. Our study confirms that, on average, birth weight was highest among singletons, medium among twins, and lowest among triplets. A marked difference in the mean birth weight between singleton males and females was found. For singletons, the distribution of birth weight differed significantly from the normal distribution, but for twins the normal distribution held.

The results presented in this paper are part of a current comparative study of genetic and environmental influences in three educational settings: Stockholm, Jerusalem and the Israeli kibbutz. We specifically wanted to investigate whether a more restrictive educational setting would decrease genetic influences. Here we report on comparisons of cognitive performance measures at several time points for twins/controls, boys/girls and within-pair similarity in MZ, DZ and controls. The tests used were the Raven Progressive Matrices, verbal, reading comprehension and arithmetic. The results show no differences between twins and controls, whilst gender differences seem to be smallest in the Stockholm sample and largest in Jerusalem. A pattern of genetic influences on cognitive performance was also clearly visible in Jerusalem. In Stockholm shared environmental influences at home and at school seemed even stronger than in the kibbutz. No consistent differences were found between tests or occasions.

Adverse events during the perinatal period have traditionally been thought to contribute to the risk of febrile seizures although an association has not been found in large epidemiological studies. Disease-discordant twins provide a means to assess the role of non-shared environmental factors while matching for confounding factors and avoiding difficulties of epidemiological studies in singletons. This study aimed to examine the association of obstetric events and febrile seizures in a community-based twin study. Twenty-one twin pairs discordant for febrile seizures were ascertained from a community-based twin register. Obstetric events were scored using the McNeil-Sjöström Scale for Obstetric Complications and expressed as a summary score (OC score). The frequency of individual obstetric events in affected and unaffected twins, the within-pair differences in OC scores and other markers of perinatal risk including birthweight, birth order and Apgar scores were examined. No significant difference was found in the frequency of individual obstetric events, nor in OC scores between affected and unaffected twins. No differences in birth weight, birth order, 1- or 5-minute Apgar scores were observed. Our results confirm previous findings that obstetric events are not associated with the risk of febrile seizures.

Ethnicity differences account for genetic, environmental, lifestyle, and reproductive variables, influencing the rate of twinning (Nylander, 1981). Frequently, ethnic differences correlate with variable perinatal care leading to differences in outcome. Free access to antenatal care, and to facilities for delivery and neonatal care is available for the entire population in Israel, and therefor differences attributed to levels of medical care are practically negligible. We previously evaluated the overall relationship between ethnicity and outcome in a popula-tion-based cohort of mothers of twins (Goldman et al., 2001). However, the overall comparison may have masked some differences that could be present. The purpose of this study was to evaluate whether ethnicity is associated with differences in perinatal outcome in randomly selected, matched-controlled Israeli Jewish and Muslim mothers of twins.

The Human Genetics Society of Australasia is a vibrant professional society with more than 900 members that promotes and regulates the practice of human and medical genetics in Australia and New Zealand. The growth of human genetics was stimulated by the development of diagnostic clinical cytogenetics laboratories in the early to mid 1960s. This coincided with the recognition by medical specialists, mainly pediatricians, that genetic disorders, especially inborn errors of metabolism and birth defects, were of clinical interest and potentially challenging areas for their skills. The organization of professionals in human genetics was slow to evolve. There was an early Western Australian Human Genetics Society, and the cytogenetics community had begun to meet annually from about 1966 but was coordinated by a mailing list rather than as a formal organization. In 1976, as part of the celebrations of the Centenary Year of the Adelaide Children's Hospital, a clinical genetics meeting involving several high profile international speakers and most of the senior medical geneticists in Australia and New Zealand along with the annual meeting of the loose-knit cytogeneticists group agreed that a small working group be charged with setting up a Human Genetics Society. The society was formally incorporated in South Australia in 1977.

Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.

Colorectal cancer is the third most common and second most deadly type of cancer worldwide, with approximately 1.9 million cases and 0.9 million deaths worldwide in 2020. Previous studies have shown that estrogen and testosterone hormones are associated with colorectal cancer risk and mortality. However, the potential effect of their precursor, dehydroepiandrosterone sulfate (DHEAS), on colorectal cancer risk has not been investigated. Therefore, evaluating DHEAS’s effect on colorectal cancer will expand our understanding of the hormonal contribution to colorectal cancer risk. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal effect of DHEAS on colorectal cancer. We obtained DHEAS and colorectal cancer genomewide association study (GWAS) summary statistics from the Leipzig Health Atlas and the GWAS catalog and conducted MR analyses using the TwoSampleMR R package. Our results suggest that higher DHEAS levels are causally associated with decreased colorectal cancer risk (odds ratio per unit increase in DHEAS levels z score = 0.70; 95% confidence interval [0.51, 0.96]), which is in line with previous observations in a case–control study of colon cancer. The outcome of this study will be beneficial in developing plasma DHEAS-based biomarkers in colorectal cancer. Further studies should be conducted to interpret the DHEAS-colorectal cancer association among different ancestries and populations.

Neurophysiological measurements of the response to pre-pulse and startle stimuli have been suggested to represent an important endophenotype for both substance dependence and other select psychiatric disorders. We have previously shown, in young adult Mexican Americans (MA), that presentation of a short delay acoustic pre-pulse, prior to the startle stimuli can elicit a late negative component at about 400 msec (N4S), in the event-related potential (ERP), recorded from frontal cortical areas. In the present study, we investigated whether genetic factors associated with this endophenotype could be identified. The study included 420 (age 18–30 years) MA men (n = 170), and women (n = 250). DNA was genotyped using an Affymetrix Axiom Exome1A chip. An association analysis revealed that the CCKAR and CCKBR (cholecystokinin A and B receptor) genes each had a nearby variant that showed suggestive significance with the amplitude of the N4S component to pre-pulse stimuli. The neurotransmitter cholecystokinin (CCK), along with its receptors, CCKAR and CCKBR, have been previously associated with psychiatric disorders, suggesting that variants near these genes may play a role in the pre-pulse/startle response in this cohort.

In this exploratory study of 15 families with a twin-pair, of which one has an intellectual disability, the Nijmegen Questionnaire on Childrearing Situations (NQCS) was used to ask mothers about their perceptions and experiences of parenting. An interview with the mothers was done to understand the initial stages of coping with this double problem: educating a twin-pair and a child with an intellectual disability. Four groups of mothers were identified, depending on whether they accepted the intellectual disability of their child and/or whether they perceived their children as a twin-pair or not. Finally, some critical questions for further research and management were formulated.

Co-twin comparisons address familial confounding by controlling for genetic and environmental influences that twin siblings share. We applied the co-twin comparison design to investigate associations of adolescent factors with alcohol dependence (AD) symptoms. Participants were 1286 individuals (581 complete twin pairs; 42% monozygotic; and 54% female) from the FinnTwin12 study. Predictors included adolescent academic achievement, substance use, externalizing problems, internalizing problems, executive functioning, peer environment, physical health, relationship with parents, alcohol expectancies, life events, and pubertal development. The outcome was lifetime AD clinical criterion count, as measured in young adulthood. We examined associations of each adolescent domain with AD symptoms in individual-level and co-twin comparison analyses. In individual-level analyses, adolescents with higher levels of substance use, teacher-reported externalizing problems at age 12, externalizing problems at age 14, self- and co-twin-reported internalizing problems, peer deviance, and perceived difficulty of life events reported more symptoms of AD in young adulthood (ps < .044). Conversely, individuals with higher academic achievement, social adjustment, self-rated health, and parent–child relationship quality met fewer AD clinical criteria (ps < .024). Associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, self-rated health, and AD symptoms were of a similar magnitude in co-twin comparisons. We replicated many well-known adolescent correlates of later alcohol problems, including academic achievement, substance use, externalizing and internalizing problems, self-rated health, and features of the peer environment and parent–child relationship. Furthermore, we demonstrate the utility of co-twin comparisons for understanding pathways to AD. Effect sizes corresponding to the associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, and self-rated health were not significantly attenuated (p value threshold = .05) after controlling for genetic and environmental influences that twin siblings share, highlighting these factors as candidates for further research.

Monochorionic twin pregnancies are subject to unique complications that can threaten the life and well-being of both fetuses, resulting in a disproportionate increase in perinatal morbidity and mortality.

While the true figures are not well established, outcomes of twin pregnancies are directly dependent on a small number of preterm births between 22 and 27 weeks. Observation of perinatal outcomes in twin pregnancies yields two contradictory results. Firstly, it shows an improvement in perinatal mortality figures. Secondly, it reveals an increase in the rates of preterm deliveries. These findings result from the observation of 783 twin pregnancies followed and delivered in a level 3 perinatal centre in Paris between 1993 and 1998. Women followed since the beginning of pregnancy through the outpatient clinic of the institution are included in this number, as are women who were referred or transferred to the centre at a later date due to complications. This analysis reflects the influence of two contrasting policies. The first, and less recent policy is devoted to the prevention of preterm births, and is reflected by the low number of extremely preterm deliveries at 22–32 weeks. The second is the effect of our new approach to the prevention of foetal deaths in relation to foetal growth retardation in twins which has resulted in increased medical intervention such as the induction of labour or scheduled Caesarean birth. This has resulted in an increase in twin preterm births from 33 to 36 weeks, with the expected result of fewer foetal deaths.

The long-term effect of differences in placentation in MZ twins is a controversial subject. An effect has been clearly established for birth weight but data on psychological traits are still under debate. We studied 20 pairs of monochorionic MZ (MCMZ) and 24 pairs of dichorionic MZ (DCMZ) twins. A chorion effect was observed for Block Design (WISC-R) confirming a previous report: MC MZ co-twins were more similar that DC MZ co-twins. For anthropometrical measures, an expected effect in the opposite direction was found. No chorion effect was significant for the other variables. A follow up was undertaken 3 years later using cognitive, national academic evaluations, and personality variables. The sample included 16 pairs of MC MZ and 22 pairs of DC MZ twins. Again a chorion effect was observed on anthropometrical variables but results on the Block Design were not replicated. However, the MC MZ co-twins were more similar than the DC MZ co-twins for two other cognitive variables: Perceptual Organization Index from the WISC-R and Global Visualisation from a Belgian reasoning test. Among the personality variables only one was sensitive to a chorion effect. The discussion focuses on the need for larger samples to achieve adequate power in statistical comparisons.