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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]

The Australian Twin Registry (ATR) is a national volunteer resource of twin pairs and higher-order multiples willing to consider participating in health, medical, and scientific research. The vision of the ATR is ‘to realize the full potential of research involving twins to improve the health and well-being of all Australians’. The ATR has been funded continuously by the National Health and Medical Council for more than 30 years. Its core functions entail the recruitment and retention of twin members, the maintenance of an up-to-date database containing members’ contact details and baseline information, and the promotion and provision of open access to researchers from all institutes in Australia, and their collaborators, in a fair and equitable manner. The ATR is administered by The University of Melbourne, which acts as custodian. Since the late 1970s the ATR has enrolled more than 40,000 twin pairs of all zygosities and facilitated more than 500 studies that have produced at least 700 peer-reviewed publications from classical twin studies, co-twin control studies, within-pair comparisons, twin family studies, longitudinal twin studies, randomized controlled trials, and epigenetics studies, as well as studies of issues specific to twins. New initiatives include: a Health and Life Style Questionnaire; data collection, management, and archiving using a secure online software program (The Ark); and the International Network of Twin Registries. The ATR's expertise and 30 years of experience in providing services to national and international twin studies has made it an important resource for research across a broad range of disciplines. [ABSTRACT FROM AUTHOR]

The Peri/postnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250 pairs of Australian twins and their mothers, who were recruited mid-way through pregnancy from January 2007 to September 2009. The study is centered on the developmental origins of health and disease paradigm (DOHaD) in which an adverse intrauterine environment predisposes the individual to complex disease in later life by reducing growth in utero and adversely altering developmental plasticity. Data concerning diet and lifestyle were collected from mothers during pregnancy, and samples of plasma and serum taken at 28 weeks’ gestation. We attended 75% of all births, at which time we collected multiple biological samples including placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs. Chorionicity was recorded and zygosity was determined by DNA testing where necessary. Approximately 40% of the twins are monozygotic, two-thirds of which are dichorionic. Twins were seen again at 18 months of age and repeat blood and cheek swabs taken where possible. Studies of gene expression and the epigenetic marks of DNA methylation have so far revealed that twins exhibit a wide range of epigenetic discordance at birth, that one-third of the epigenome changes significantly between birth and 18 months; shared (maternal) environment, genetic factors, and non-shared intrauterine environment contribute to an increasing proportion of epigenetic variation at birth, respectively, and affect tissues differently, and that within-pair birth weight discordance correlates with epigenetic discordance in genes associated with lipid metabolism, supporting an epigenetic mechanism for DOHaD. [ABSTRACT FROM AUTHOR]

BackgroundThree cognitive constructs are risk factors for eating disorders: undue influence of weight and shape, concern about weight and shape, and body dissatisfaction (BD). Undue influence, a diagnostic criterion for eating disorders, is postulated to be closely associated with self-esteem whereas BD is postulated to be closely associated with body mass index (BMI). We understand less about the relationships with concern about weight and shape. The aim of the current investigation was examine the degree of overlap across these five phenotypes in terms of latent genetic and environmental risk factors in order to draw some conclusions about the similarities and differences across the three cognitive variables.MethodA sample of female Australian twins (n=1056, including 348 complete pairs), mean age 35 years (s.d.=2.11, range 28–40), completed a semi-structured interview about eating pathology and self-report questionnaires. An independent pathways model was used to investigate the overlap of genetic and environmental risk factors for the five phenotypes.ResultsIn terms of variance that was not shared with other phenotypes, self-esteem emerged as being separate, with 100% of its variance unshared with the other phenotypes, followed by undue influence (51%) and then concern (34%), BD (28%) and BMI (32%).ConclusionsIn terms of shared genetic risk, undue influence and concern were more closely related than BD, whereas BMI and BD were found to share common sources of risk. With respect to environmental risk factors, concern, BMI and BD were more closely related to each other than to undue influence. [ABSTRACT FROM PUBLISHER]

The objective of the current study was to investigate the heritability of breast size and the degree to which this heritability is shared with BMI. In a sample of 1010 females twins (mean age 35 years; SD = 2.1; range 28-40), self-report data pertaining to bra cup size and body mass index (BMI) was collected in the context of self-report data and an interview relating to disordered eating respectively. In a sample of 348 complete twin pairs who completed data collection (226 MZ pairs and 122 DZ pairs and 360 incomplete pairs (170 MZ and 190 DZ)), we found that the heritability of bra cup size was 56%. Of this genetic variance, one third is in common with genes influencing body mass index, and two thirds (41% of total variance) is unique to breast size, with some directional evidence of non-additive genetic variation. The implications of these findings with respect to previous research linking breast size with reproductive potential are discussed. [ABSTRACT FROM AUTHOR]

Abstract This study employs multiple regression models based on DeFries and Fulker (1985), and a large sample of twins, to assess heritability in attitudes towards economic risk, and the extent to which this heritability differs between males and females. Consistent with Cesarini et al. (2009), it is found that attitudes towards risk are moderately heritable, with about 20 percent of the variation in these attitudes across individuals being linked to genetic differences. This value is less than one-half the estimates reported by Zyphur et al. (2009) and Zhong et al. (2009). While females are more risk averse than males, there is no evidence that heritability in attitudes towards risk differs between males and females. Even though heritability is shown to be important to economic risk-taking, the analyses suggest that multivariate studies of the determinants of attitudes towards risk which to not take heritability into consideration still provide reliable estimates of the partial effects of other key variables, such as gender and educational attainment. [ABSTRACT FROM AUTHOR]

We examined the variation and heritability of DSM-IV nicotine withdrawal (NW) in adult and adolescent male and female twin cigarette smokers (who reported smoking 100 or more cigarettes lifetime). Telephone diagnostic interviews were completed with 3,112 Australian adult male and female smokers (53% women; age: 24-36) and 702 Missouri adolescent male and female smokers (59% girls; age: 15-21). No gender or cohort differences emerged in rates of meeting criteria for NW (44%). Latent class analyses found that NW symptoms were best conceptualized as a severity continuum (three levels in adults and two levels in adolescents). Across all groups, increasing NW severity was associated with difficulty quitting, impairment following cessation, heavy smoking, depression, anxiety, conduct disorder and problems with alcohol use. NW was also associated with seeking smoking cessation treatment and with smoking persistence in adults. The latent class structure of NW was equally heritable across adult and adolescent smokers with additive genetic influences accounting for 49% of the variance and the remaining 51% of variance accounted for by unique environmental influences. Overall, findings suggest remarkable similarity in the pattern and heritability of NW across adult and adolescent smokers, and highlight the important role of NW in psychiatric comorbidity and the process of smoking cessation across both age groups. [ABSTRACT FROM AUTHOR]

The genetic basis of cardiovascular disease (CVD) is complex and still largely elusive. Plasma lipid concentrations are well-established risk factors for cardiovascular disease (CVD), and have adult heritabilities ranging from 0.48 to 0.87. Estimates for adolescents are slightly higher (range 0.71 to 0.82). To identify loci affecting lipid concentrations across adolescence, we analyzed longitudinal lipid data in a sample of 134 monozygotic and 626 dizygotic twin pairs at ages twelve, fourteen and sixteen, and their siblings, from 760 Australian families. Univariate linkage analysis for each phenotype and time point was supplemented by multivariate analysis across the time points. A genome-wide association scan was also performed on a subset of the subjects (N = 441). The strongest linkage was seen for triglycerides on chromosome 6p24.3 (multivariate -log(10) p = 6.81; equivalent LOD = 6.13; p = 1.55 x 10(-7)). Significant linkage was also found for LDL cholesterol on chromosome 2q35 (multivariate -log(10)p = 5.59; equivalent LOD = 4.53; p = 2.57 x 10(-6)). In the association analysis, rs10503840 on 8p21.1 was significantly associated with total cholesterol levels at age fourteen (p = 8.24 x 10(-7), estimated significance threshold 2.45 x 10(-6)). Association at p < 2.25 x 10(-6) was also found between triglycerides at age 12 and rs10507266, in an intron of THRAP2 (MIM 608771) on 12q24.21; and between HDL-C at age 14 and rs10506325 in an intergenic region of 12q13.13. Suggestive evidence of association at ages twelve and fourteen was found between HDL-C and rs10492859 on 16q23 (p = 2.42 x 10(-5) and 2.77 x 10(-4), respectively). Further longitudinal genetic studies of cardiovascular risk factors, focused on critical periods of development or change, are needed. [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]

This article describes the Australian Twin Attention-deficit/hyperactivity disorder (ADHD) Project (ATAP), the results of research conducted using this database and plans for future studies. Information has been actively collected from Australian families with twin children since 1991 for the ATAP database. The value of assessing siblings as well as twins is emphasized. Much work has gone into continuing the involvement of families in the study though this does become more difficult when twins reach maturity. The main focus of the project is ADHD in children and adolescents plus comorbid conditions including conduct disorder, oppositional defiant disorder, and generalized anxiety disorder. A major challenge has been how to retain continuity in the assessments, while at the same time covering changes in psychiatric classification, such as the move to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994). Changes in the scale can affect the reports of twin similarity. Over the years, these twins have become part of other twin studies and future plans include linking different twin databases to investigate the relationships between childhood behavior and adult conditions. Recruitment, assessment and retention of twin families require a major commitment but create a significant resource for collaboration in areas outside the original aim. [ABSTRACT FROM AUTHOR]

The Australian Twin Registry (ATR) has, since the late 1970s, enrolled more than 30,000 pairs of all zygosity types and ages willing to consider participation in approved research studies. Its core functions are the recruitment to, and maintenance of, an up-to-date database containing contact details and baseline information, and the management of fair and equitable access so as to enhance medical and scientific research. The ATR has facilitated more than 430 studies producing 525 peer-reviewed publications using a variety of designs including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. The ATR is supported for 2004 to 2009 by an Australian National Health and Medical Research Council (NHMRC) Enabling Grant, a new form of funding which recognizes the importance of long-term support for shared national resources. New initiatives include: integration with the Western Australian Twin Child Health (WATCH) cohort and the new Western Australian Twin Registry (WATR); foundation of a cohort of mothers and their twin children recruited from the time of diagnosis of the multiple gestation (match); a national Twins Festival run in collaboration with the Australian Multiple Birth Association (AMBA); promotion of the ATR at medical conferences; and fostering an active network of researchers from a range of disciplines and providing financial support for new researchers to attend international twin research workshops. Consistent with its mission statement, the long-term goal of the ATR is to make twin studies a standard component of medical and scientific research. [ABSTRACT FROM AUTHOR]