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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]

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]

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]

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]

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]