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Background and Aims: Previous studies have demonstrated associations between substance use and reduced educational attainment; however, many were unable to account for potential confounding factors like genetics and the rearing environment. In the few studies that controlled for these factors, the substances assessed were limited to alcohol, cannabis, and tobacco. To address these limitations, we examined the relationship between adolescent use of seven kinds of substances, the number of additional substances used, and high school noncompletion within a large sample of Australian twins. Design: A series of two‐level generalized mixed effects logistic regressions were conducted to examine associations between adolescent substance use and high school noncompletion. Setting: Australia. Participants: A total of 9579 adult Australian twins from two cohorts of the Australian Twin Registry. Measurements Assessments of high school completion, childhood major depression, conduct disorder symptoms, substance use initiation, demographics, and parental educational attainment using the Australian version of the Semi‐Structured Assessment for the Genetics of Alcoholism. Findings There were unique within‐twin‐pair effects of use of sedatives (odds ratio [OR] = 22.39 [95% confidence interval (CI) = 1.18–423.48]) and inhalants/solvents (OR = 10.46 [95% CI = 1.30–84.16]) on high school noncompletion. The number of substances used in adolescence was strongly associated with high school noncompletion across all discordant twin models (ORs from 1.50–2.32, Ps < 0.03). Conclusions: In Australia, adolescent substance use appears to be associated with early school dropout, with the effects of any given substance largely because of the confounding factors of parental education, childhood conduct disorder symptoms, and use of other substances. Sedatives and inhalants/solvents have effects on high school noncompletion that cannot be explained by polysubstance use or familial factors. [ABSTRACT FROM AUTHOR]

Aims: To identify drug use typologies based on substances used and persistence of use over two time points, use a genetically informed design to explore twin concordance of and genetic influence on the use typologies and compare patterns of declined/discontinued ("desistant") and persistent drug use on drug use correlates. Design Latent class analysis was applied to data from a cross‐sectional self‐report survey on current and past drug use. Use characteristics, use disorder, and psychiatric problems were compared across classes. Setting: Computer‐assisted telephone interview in respondents' homes. Participants: A total of 3785 individual twins and siblings (1365 men, 2420 women; Mage = 32) from the Australian Twin Registry Cohort III. Measurements A comprehensive interview assessed prior to past year and past year use of cannabis, stimulants, cocaine/crack, hallucinogens, opioids, sedatives, inhalants, dissociatives, and solvents; age of first use; opportunity to use; peer drug use; attention deficit/hyperactivity, conduct, antisocial personality, depressive, and substance use disorders; and suicidality. Findings A five‐class solution emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%). Twin concordances were higher among monozygotic (k = 0.30–0.35) than dizygotic pairs (same‐sex k = 0.19–0.20; opposite sex k = 0.07), and biometric modeling suggested that the persistent polydrug use class, in particular, was highly heritable (a2 = 0.94). Conduct disorder (OR = 2.40), antisocial personality disorder (OR = 3.27), and suicidal ideation (OR = 1.98) increased persistent polydrug use risk; depression (OR = 2.38) and lifetime suicide attempt (OR = 2.31) increased persistent prescription misuse risk. Relative to persistent prescription drug misuse, persistent polydrug use was associated with higher rates of cannabis and stimulant use disorder (OR = 6.14–28.01), younger first substance use (OR = 0.82–0.83), more drug use opportunity (OR = 10.66–66.06), and more drug‐using peers (OR = 4.66–9.20). Conclusions: Unique patterns of declined/discontinued ("desistant") and persistent drug use are differentially heritable and differentially associated with risk factors, psychiatric symptoms, and substance use disorder outcomes. [ABSTRACT FROM AUTHOR]

Mortality risk is known to be associated with many physiological or biochemical risk factors, and polygenic risk scores (PRSs) may offer an additional or alternative approach to risk stratification. We have compared the predictive value of common biochemical tests, PRSs and information on parental survival in a cohort of twins and their families. Common biochemical test results were available for up to 13,365 apparently healthy men and women, aged 17-93 years (mean 49.0, standard deviation [SD] 13.7) at blood collection. PRSs for longevity were available for 14,169 study participants and reported parental survival for 25,784 participants. A search for information on date and cause of death was conducted through the Australian National Death Index, with median follow-up of 11.3 years. Cox regression was used to evaluate associations with mortality from all causes, cancers, cardiovascular diseases and other causes. Linear relationships with all-cause mortality were strongest for C-reactive protein, gamma-glutamyl transferase, glucose and alkaline phosphatase, with hazard ratios (HRs) of 1.16 (95% CI [1.07, 1.24]), 1.15 (95% CI 1.04-1.21), 1.13 (95% CI [1.08, 1.19]) and 1.11 (95% CI [1.05, 1.88]) per SD difference, respectively. Significant nonlinear effects were found for urea, uric acid and butyrylcholinesterase. Lipid risk factors were not statistically significant for mortality in our cohort. Family history and PRS showed weaker but significant associations with survival, with HR in the range 1.05 to 1.09 per SD difference. In conclusion, biochemical tests currently predict long-term mortality more strongly than genetic scores based on genotyping or on reported parental survival. [ABSTRACT FROM AUTHOR]

Aim: To assess educational outcomes of twins and quantify the degree this is mediated by gestational age and other perinatal factors.Methods: We conducted a population-based record-linkage cohort study of all live births ≥24 weeks gestation in New South Wales, Australia with a corresponding standardised school test result for grade 3 in 2008-2014. The primary outcome was whether a child met the National Minimum Standard (NMS) cut-off in literacy and numeracy domains. Robust multivariable Poisson models were used to obtain adjusted relative risks (aRRs), and mediation analysis conducted to assess contributing factors on the causal pathway.Results: Of 351 791 liveborn infants, 10 365 (2.9%) were twins. After adjusting for maternal covariates and compared with singletons, twins had an increased risk of not meeting the NMS for all five literacy and numeracy domains (aRR 1.27-1.45, P < .001). Gestational age alone mediated up to 73% of aRRs and small for gestational age further attenuated these effects with only minimal risk remaining after adjusting for all mediators (aRR 0.94-1.07).Conclusion: Almost all of the educational disadvantage experienced by twins, compared with singletons, is attributable to the risk associated with shorter gestational age, and partly by poor foetal growth. These findings support efforts to prolong gestation of twin pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between inter‐twin delivery interval and short‐term perinatal outcomes of the second twin after vaginal delivery of the first twin. Methods: Retrospective cohort study including twin pregnancies with a vaginal delivery of the first twin between January 2011 and September 2017 in a tertiary hospital in Melbourne, Australia. The main outcome measure was a composite of adverse neonatal outcome (at least one of perinatal death, admission to neonatal intensive care unit (NICU), endotracheal intubation, Apgar <7 at five minutes and cord lactate >4.0 mmol/L). Proportions of adverse outcomes for the second twin were compared between groups of intervals ≤ or >10 and ≤ or >30 min. Results: The composite adverse neonatal outcome occurred in 201 (58.2%) and a caesarean section occurred in seven cases (2%) of the 345 pregnancies included. Delivery interval was associated with higher cord lactate. Low Apgar scores were more frequent with intervals >30 min (17.9% vs 6.6%, P = 0.03), as well as caesarean section for the second twin (10.7% vs 1.3%, P = 0.01). Composite adverse outcome and admission to NICU were not significantly influenced by the delivery interval. Predictors of adverse outcome were gestational age, abnormal cardiotocography and breech delivery of the second twin. Conclusion: The inter‐twin delivery interval is associated with higher rates of low Apgar scores and higher cord lactate for the second twin. These associations do not translate into higher rates of admission to NICU and their long‐term clinical implications are uncertain. [ABSTRACT FROM AUTHOR]

Background: Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences. Methods: Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project. Results: The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [ r G = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [ r G = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [ r E = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females. Conclusions: Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma. [ABSTRACT FROM AUTHOR]

Background and aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi‐substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. Methods: A twin‐based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome‐wide association meta‐analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. Results: The twin‐based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19–60%]. Shared and unique environmental factors explained 39% (95% CI = 20–56%) and 22% (95% CI = 16–29%). The genome‐wide association meta‐analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium‐transporting ATPase gene (ATP2C2) at P < 5E‐08. All five SNPs are in high linkage disequilibrium (LD) (r2 > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E‐09). Gene‐based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e‐06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP‐based heritability for age at first cannabis use was non‐significant. Conclusion: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders. [ABSTRACT FROM AUTHOR]

The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies. [ABSTRACT FROM PUBLISHER]

Objective: Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early cannabis use and NSSI and to examine genetic and environmental mechanisms of this association.Method: Adult male and female twins from the Australian Twin Registry (N = 9,583) were used to examine the odds of NSSI associated with lifetime cannabis use and early cannabis use (i.e., <17 years of age). These associations were also examined within monozygotic (MZ) twins discordant for cannabis use and MZ twins discordant for early cannabis use. Analyses were replicated in an independent sample of female twins (n = 3,787) accounting for the age at onset of cannabis use and NSSI.Results: Lifetime cannabis use (odds ratio [OR] = 2.84, 95% CI [2.23, 3.61]) and early cannabis use were associated with increased odds of NSSI (OR = 2.15, 95% CI [1.75, 2.65]), and this association remained when accounting for covariates. The association was only significant, however, in MZ twin pairs discordant for early cannabis use (OR = 3.20, 95% CI [1.17, 8.73]). Replication analyses accounting for the temporal ordering of cannabis use and NSSI yielded similar findings of nominal significance.Conclusions: Results suggest that NSSI is associated with cannabis involvement via differing mechanisms. For lifetime cannabis use, the lack of association in discordant pairs suggests the role of shared genes and family environment. However, in addition to such shared familial influences, person-specific and putatively causal factors contribute to the relationship between early cannabis use and NSSI. Therefore, delaying the onset of cannabis use may reduce exposure to influences that exacerbate vulnerabilities to NSSI. [ABSTRACT FROM AUTHOR]

Aim The purpose of this study was to investigate neonatal outcome of dichorionic diamniotic twins born beyond 32 weeks' gestation according to mode of delivery at a major tertiary center in Australia. Methods This was a retrospective cohort study of women with dichorionic diamniotic twins delivering at ≥32 weeks' gestation at a large tertiary maternity center in Australia using data from a maternity database. Primary and secondary outcomes included mode of delivery, birthweight, stillbirth, Apgar score, neonatal unit admission, neonatal resuscitation, death and respiratory distress. Results Of 1261 women, 82.9% (1045/1261; 2090 babies) delivered at ≥32 weeks' gestation. The mode of delivery for these babies was as follows: normal vaginal delivery, 419 (20%); instrumental delivery, 179 (8.6%); emergency cesarean section, 658 (31.5%); and elective cesarean section, 834 (39.9%). Babies delivered by emergency cesarean section or instrumental vaginal delivery had worse outcome. In contrast, the lowest complications were seen in the uncomplicated vaginal delivery and elective cesarean section cohorts. Conclusions Neonatal outcome was worse for those delivering via emergency cesarean section or instrumental vaginal delivery compared with elective cesarean section or uncomplicated vaginal delivery. The rate of uncomplicated vaginal delivery, however, was low, with only 14.8% of women delivering both babies vaginally without any form of intervention. [ABSTRACT FROM AUTHOR]

This study sought to identify distinct trajectory classes of growth of disordered eating (DE), and their respective correlates and risk factors. Females ages 12-19 years (Australian Twin Registry) were interviewed by telephone with the Eating Disorder Examination on 3 occasions (Wave 1: N = 699; Wave 2: N = 669; Wave 3: N = 499). Each participant also completed self-report measures across all waves, and their parents at Waves 1 and 2. Growth mixture modeling determined the optimal classes representing DE growth trajectories over 3 data-points. The best fit was a 3-class solution constituting: (a) no growth in DE over time (90%; low-static) where 10% reported a lifetime eating disorder (ED); (b) a high intercept but decreasing over time (7%; 53% had a lifetime ED; attenuating); (c) an increasing level of DE (3%; 80% experiencing a lifetime ED; escalating). The majority (64%) of EDs in the attenuating group were diagnosed at Wave 1, whereas 84% of EDs in the escalating group were diagnosed at subsequent waves. The low-static group had fewest significant correlates/risk factors for DE. A multivariable GEE identified that over adolescence, internalization of the thin ideal was 2.5 times more likely characterize an escalating rather than low-static DE symptom trajectory. These findings underscore the fundamental importance of concentrating efforts on reducing the potency of the thin ideal message, and strategies directed toward resolving life stressors by effective management of emotion and problem resolution, in order to prevent the development of DE. [ABSTRACT FROM AUTHOR]

Background.Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses.Method.Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24–37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder.Results.Additive genetic (a2 = 0.48–0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a2 = 0.39) and shared environmental (c2 = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38–0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40–73% of the genetic variance per substance.Conclusions.Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols. [ABSTRACT FROM PUBLISHER]

BackgroundWe investigated the genetic and environmental contributions to disordered eating (DE) between early and late adolescence in order to determine whether different sources of heritability and environmental risk contributed to these peak times of emergence of eating disorders.MethodAdolescent female twins from the Australian Twin Registry were interviewed over the telephone with the Eating Disorder Examination (EDE). Data were collected at 12–15 and 16–19 years (wave 1: N = 699, 351 pairs; wave 3: N = 499, 247 pairs). Assessments also involved self-report measures related to negative life events and weight-related peer teasing.ResultsUnstandardized estimates from the bivariate Cholesky decomposition model showed both genetic influences and non-shared environmental influences increased over adolescence, but shared environmental influences decreased. While non-shared environmental sources active at ages 12–15 years continued to contribute at 16–19 years, new sources of both additive genetic and non-shared environmental risk were introduced at ages 16–19 years. Weight-related peer teasing in early-mid adolescence predicted increases of DE in later adolescence, while negative life events did not.ConclusionsTwo-thirds of the heritable influence contributing to DE in late adolescence was unique to this age group. During late adolescence independent sources of genetic risk, as well as environmental influences are likely to be related in part to peer teasing, appear key antecedents in growth of DE. [ABSTRACT FROM PUBLISHER]

ABSTRACT Objective There is a high level of co-occurrence of suicidality with eating disorders (EDs) but the reason for this is unknown. To test the hypothesis that suicidality and EDs share genetic risk contributing to the expression of both phenotypes. Method Female twins ( N = 1,002) from the Australian Twin Registry, aged 28-40 years, were interviewed with diagnostic interviews. Lifetime diagnostic information relating to eating disorders [anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder, and purging disorder (PD)], suicidality (ranging transitory thoughts to suicide attempts), and major depression. Results Any suicidal thoughts were reported by 24% of the sample, but prevalence of lifetime suicidality among female twins with EDs was much higher (43%), presence of an ED diagnosis more than doubling likelihood of suicidality (OR = 2.32, 95% CI: 1.63-3.31). AN and BN conveyed greatest risk of suicidality (OR = 2.03, 95% CI: 1.06-3.87; OR = 3.97, 95% CI: 2.01-7.85, respectively). Twin phenotype correlations showed monozygotic twins had uniformly higher estimates than dizygotic counterparts. A trivariate Cholesky model indicated a common genetic influence on suicidality and ED phenotypes (but not depression), and no nonshared environmental source. Discussion Both cross twin phenotypic correlations and genetic modeling infer a common genetic pathway for suicidality and EDs, but further investigation is needed to elucidate whether this may constitute emotional dysregulation or other temperament-linked factors. Study findings also indicate that ED clients must be routinely assessed for presence of suicidality, independent of depression status. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:684-691) [ABSTRACT FROM AUTHOR]

ABSTRACT Objective The recent DSM-5 categorization of eating disorders introduces a new category of eating disorders, Unspecified Feeding and Eating Disorders (UFED), where symptoms do not meet criteria for any other diagnostic category, but cause clinically significant distress or impairment. The aim of the current study was to explore what disorders in UFED might look like in an adolescent population. Method We examined a large cohort of adolescent female twins ( N = 699) who were assessed on three occasions and who did not meet a DSM-5 eating disorder diagnosis but who reported threshold levels of either fasting and/or driven exercise ( N = 33; 4.7%). This group of girls was compared to girls who reported no eating disorder over the three waves, and girls who met a diagnosis of either anorexia nervosa (AN) or atypical AN. Results The UFED group was characterized as being in the overweight range while striving to lose weight, and placing a high degree of importance on weight and shape in their self-evaluation. This group was indistinguishable from the two eating disorder groups on measures of global eating disorder severity, and demonstrated significantly elevated impairment and distress compared to the no eating disorder group commensurate with the eating disorder groups. Discussion Further research of this group is necessary to ensure that these individuals are not overlooked, and that treatment options are appropriate and available. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:367-374) [ABSTRACT FROM AUTHOR]

Cohort studies are essential for conducting large studies of multiple exposures and outcomes in humans. Recently, the ability to combine data from multiple cohorts in, for example, meta-analyses, and the willingness in the genetics community to collaborate to enable replication studies has led to many new insights into the genetic and environmental determinants of human health and behaviors. The contribution of Professor Nicholas Martin to the development of cohort studies, particularly of twin and twin-family studies, over a period of several decades is reviewed. He has contributed to the development and use of both Australian and international resources. The contributions of Australian twin studies to genomewide association projects are multiple, and across multiple domains, from biomarkers, lifestyle and behavior to disorders and disease. [ABSTRACT FROM AUTHOR]