DNA methylation analysis using bisulphite-based amplicon sequencing of individuals exposed to maternal tobacco use during pregnancy, and offspring conduct problems in childhood and adolescence.

Maternal tobacco smoking during pregnancy is a large driver of health inequalities and a higher prevalence of conduct problem (CP) has been observed in exposed offspring. Further, maternal tobacco use during pregnancy can also alter offspring DNA methylation. However, currently, limited molecular evidence has been found to support this observation. Thus we aim to examine the association between maternal tobacco use in pregnancy and offspring CP, to determine whether offspring CP is mediated by tobacco exposure-induced DNA methylation differences. Understanding the etiology of the association between maternal tobacco use and offspring CP will be crucial in the early identification and treatment of CP in children and adolescents. Here, a sub group of N =96 individuals was sourced from the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years in New Zealand. Whole blood samples underwent bisulphite-based amplicon sequencing at 10 loci known to play a role in neurodevelopment, or which had associations with CP phenotypes. We identified significant (P CYP1A1 , ASH2L and MEF2C in individuals with CP who were exposed to tobacco in utero . We conclude that environmentally-induced DNA methylation differences could play a role in the observed link between maternal tobacco use during pregnancy and childhood/adolescent CP. However, larger sample sizes are needed to produce an adequate amount of power to investigate this interaction further.

Attitudes towards cannabis and cannabis law change in a New Zealand birth cohort.

AIMS: Personal cannabis use is common across New Zealand, and an upcoming referendum will enable the public to vote on whether this should be legalised. The present research aimed to examine the attitudes of midlife New Zealand adults on cannabis use and legalisation, and to identify potential predictors of those attitudes. METHODS: At age 40, 899 participants drawn from the Christchurch Health and Development Study were interviewed about the perceived harmfulness of cannabis use, opinions on legalisation for recreational use and supply, and the use of cannabis for medicinal purposes. In addition, a range of potential predictors of legislative attitudes were examined. RESULTS: We identified a wide range of attitudes across the cohort, however the majority tended to hold a neutral view. More than 80% of the cohort expressed support for medicinal cannabis, while 47.8% supported decriminalisation, and 26.8% expressed support for legalisation for recreational use. The strongest predictors of support for legalisation were prior use of cannabis and other drugs, while additional positive predictors included a history of depression, Maori ancestry, parental drug use, novelty seeking and higher educational attainment. Predictors of more negative attitudes were also identified, and included female gender and having dependent children. CONCLUSIONS: These findings provide insight into cannabis-related views within the New Zealand context, and may help to predict voting behaviour during the 2020 Cannabis Referendum.

Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort.

Cannabis use is of increasing public health interest globally. Here we examined the effect of heavy cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study, CHDS). A total of 48 heavy cannabis users were selected from the CHDS cohort, on the basis of their adult exposure to cannabis and tobacco, and DNA methylation assessed from whole blood samples, collected at approximately age 28. Methylation in heavy cannabis users was assessed, relative to non-users (n = 48 controls) via the Illumina Infinium® MethylationEPIC BeadChip. We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenome-wide significance level (P < 10-7). However, there were 521 sites differentially methylated at P < 0.001 which were enriched for genes involved in neuronal signalling (glutamatergic synapse and long-term potentiation) and cardiomyopathy. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190, MUC3L, CDC20 and SP9). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger sample sizes are required to investigate this further.

Social Causation, Social Selection, or Common Determinants? Examining Competing Explanations for the Link Between Young Adult Unemployment and Nicotine Dependence.

INTRODUCTION: Unemployment has been related to smoking, yet the causal nature of the association is subject to continued debate. Social causation argues that unemployment triggers changes in smoking, whereas the social selection hypothesis proposes that pre-existing smoking behavior lowers the probability of maintaining employment. The present study tested these competing explanations while accounting for another alternative explanation-common liability. METHODS: Data were from the Christchurch Health and Development Study, a longitudinal cohort followed from birth to age 35. Odds were generated for having nicotine dependence in models for social causation and being unemployed in models for social selection. These models were extended to include possible common liability factors during childhood (eg, novelty seeking) and young adulthood (eg, major depression). RESULTS: In the model testing social causation, coefficients representing the impacts of unemployment on nicotine dependence remained statistically significant and robust (odds ratio [OR] = 1.55; 95% confidence interval [CI] = 1.20, 2.00), even after accounting for common determinant measures. In contrast, a reverse social selection model revealed that coefficients representing the impacts of nicotine dependence on unemployment substantially attenuated and became statistically nonsignificant as childhood factors were added (OR = 1.14; 95% CI = 0.90, 1.45). CONCLUSIONS: Unemployment may serve as inroads to nicotine addiction among young adults, not the other way, even in the context of nicotine dependence, a more impaired form of smoking that may arguably hold higher potential to generate social selection processes. This social causation process cannot be completely attributable to common determinant factors. IMPLICATIONS: It is critical to clarify whether unemployment triggers changes in smoking behaviors (ie, social causation) or vice versa (ie, social selection)-the answers to the question will lead to public health strategies with very different intervention targets to break the linkage. The current study findings favor social causation over social selection, regardless of gender, and support a needed shift in service profiles for unemployed young adults-from a narrow focus on job skills training to a more holistic approach that incorporates knowledge from addiction science in which unemployed young adults can find needed services to cope with job loss.

Unrecognised and unmet physical health problems in a national cohort of very low birthweight young adults and controls.

INTRODUCTION Young adults are often reluctant to seek medical attention. Compared with full-term controls, very low birthweight (<1500 g; VLBW) young adults may have more health problems. AIM To assess the frequency of unrecognised or unmet physical health needs during a comprehensive health and welfare assessment of a national cohort of VLBW adults born in 1986 compared with full-term controls. METHODS The VLBW cohort (n = 229; 71% of those alive) and controls (n = 100) aged 27-29 years were assessed in one University Hospital over 2 days. Physical health assessments included growth, respiratory function, blood pressure, echocardiogram, renal function, blood tests and an interview. Cranial MRI scans were performed on 150 VLBW adults and 50 controls. Significant unrecognised or unmet health needs were defined as including a body mass index (BMI) >30 plus raised fasting insulin >80 pmol/L; any two of moderate respiratory obstruction, or reduced diffusing capacity, or being a regular smoker; cardiovascular: hypertension or abnormal echocardiogram. RESULTS Among the VLBW cohort and controls; 61% versus 73% (P < 0.05) rated their overall health as very good or excellent. A general practitioner (GP) referral letter was sent for 44% VLBW adults and 38% controls, concerning metabolic problems in 20% and 17% respectively; respiratory problems in 12% and 4% (P < 0.05) respectively; cardiovascular problems in 14% and 12% respectively; abnormal renal function in 7% in both groups; and anaemia in 3% and 5% respectively. DISCUSSION Unrecognised or unmet health needs were frequent in both VLBW young adults and controls. Respiratory problems and hypertension were more frequent in the former. Continuity of care is important for VLBW adults who require a regular GP. GPs should routinely ask about gestation and birthweight and VLBW graduates should volunteer this information.

Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction.

BACKGROUND: The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. METHODS: We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance. The repeats were a highly conserved poly-AC microsatellite in the upstream promoter region of the T-box brain 1 (TBR1) gene and three previously studied STRs in the activating enhancer-binding protein 2-beta (AP2-ß) and androgen receptor (AR) genes. Where significance was found we used multiple regression to assess the influence of confounding factors. RESULTS: Carriers of the shorter, most common, allele of the AR gene's GGN microsatellite polymorphism had fewer anxiety-related symptoms, which was consistent with previous studies, but in our study this was not significant following Bonferroni correction. No associations with two repeats in the AP2-ß gene withstood this correction. A novel finding was that carriers of the minor allele of the TBR1 AC microsatellite were at higher risk of conduct problems in childhood at age 7-9 (p = 0.0007, which did pass Bonferroni correction). Including maternal smoking during pregnancy (MSDP) in models controlling for potentially confounding influences showed that an interaction between TBR1 genotype and MSDP was a significant predictor of conduct problems in childhood and adolescence (p < 0.001), and of self-reported criminal behaviour up to age 25 years (p ≤ 0.02). This interaction remained significant after controlling for possible confounders including maternal age at birth, socio-economic status and education, and offspring birth weight. CONCLUSIONS: The potential functional importance of the TBR1 gene's promoter microsatellite deserves further investigation. Our results suggest that it participates in a gene-environment interaction with MDSP and antisocial behaviour. However, previous evidence that mothers who smoke during pregnancy carry genes for antisocial behaviour suggests that epistasis may influence the interaction.

Adolescent substance use and educational attainment: An integrative data analysis comparing cannabis and alcohol from three Australasian cohorts.

BACKGROUND: The relative contributions of cannabis and alcohol use to educational outcomes are unclear. We examined the extent to which adolescent cannabis or alcohol use predicts educational attainment in emerging adulthood. METHODS: Participant-level data were integrated from three longitudinal studies from Australia and New Zealand (Australian Temperament Project, Christchurch Health and Development Study, and Victorian Adolescent Health Cohort Study). The number of participants varied by analysis (N=2179-3678) and were assessed on multiple occasions between ages 13 and 25. We described the association between frequency of cannabis or alcohol use prior to age 17 and high school non-completion, university non-enrolment, and degree non-attainment by age 25. Two other measures of alcohol use in adolescence were also examined. RESULTS: After covariate adjustment using a propensity score approach, adolescent cannabis use (weekly+) was associated with 1½ to two-fold increases in the odds of high school non-completion (OR=1.60, 95% CI=1.09-2.35), university non-enrolment (OR=1.51, 95% CI=1.06-2.13), and degree non-attainment (OR=1.96, 95% CI=1.36-2.81). In contrast, adjusted associations for all measures of adolescent alcohol use were inconsistent and weaker. Attributable risk estimates indicated adolescent cannabis use accounted for a greater proportion of the overall rate of non-progression with formal education than adolescent alcohol use. CONCLUSIONS: Findings are important to the debate about the relative harms of cannabis and alcohol use. Adolescent cannabis use is a better marker of lower educational attainment than adolescent alcohol use and identifies an important target population for preventive intervention.

Psychosocial sequelae of cannabis use and implications for policy: findings from the Christchurch Health and Development Study.

BACKGROUND: The Christchurch Health and Development Study is a longitudinal study of a birth cohort of 1265 children who were born in Christchurch, New Zealand, in 1977. This cohort has now been studied from birth to the age of 35. SCOPE OF THIS REVIEW: This article examines a series of findings from the CHDS that address a range of issues relating to the use of cannabis amongst the cohort. These issues include: (a) patterns of cannabis use and cannabis dependence; (b) linkages between cannabis use and adverse educational and economic outcomes; (c) cannabis and other illicit drug use; (d) cannabis and psychotic symptoms; (e) other CHDS findings related to cannabis; and (f) the consequences of cannabis use for adults using cannabis regularly. FINDINGS: In general, the findings of the CHDS suggest that individuals who use cannabis regularly, or who begin using cannabis at earlier ages, are at increased risk of a range of adverse outcomes, including: lower levels of educational attainment; welfare dependence and unemployment; using other, more dangerous illicit drugs; and psychotic symptomatology. It should also be noted, however, that there is a substantial proportion of regular adult users who do not experience harmful consequences as a result of cannabis use. CONCLUSIONS: Collectively, these findings suggest that cannabis policy needs to be further developed and evaluated in order to find the best way to regulate a widely-used, and increasingly legal substance.

Tobacco smoking and cannabis use in a longitudinal birth cohort: evidence of reciprocal causal relationships.

BACKGROUND: There is evidence of associations between tobacco and cannabis use that are consistent with both a classical stepping-stone scenario that posits the transition from tobacco use to cannabis use ('gateway' effect of tobacco) and with the reverse process leading from cannabis use to tobacco abuse ('reverse gateway' effect of cannabis). The evidence of direct causal relationships between the two disorders is still missing. METHODS: We analysed data from the Christchurch Health and Development Study (CHDS) longitudinal birth cohort using advanced statistical modelling to control for fixed sources of confounding and to explore causal pathways. The data were analysed using both: (a) conditional fixed effects logistic regression modelling; and (b) a systematic structural equation modelling approach previously developed to investigate psychiatric co-morbidities in the same cohort. RESULTS: We found significant (p<0.05) associations between the extent of cannabis use and tobacco smoking and vice versa, after controlling for non-observed fixed confounding factors and for a number of time-dynamic covariate factors (major depression, alcohol use disorder, anxiety disorder, stressful life events, deviant peer affiliations). Furthermore, increasing levels of tobacco smoking were associated with increasing cannabis use (p=0.02) and vice versa (p<0.001) over time. CONCLUSIONS: Our results lend support to the notion of both of 'gateway' and 'reverse gateway' effects. That is, the association between tobacco and cannabis use arises from a reciprocal feedback loop involving simultaneous causation between tobacco use disorder and cannabis use disorder.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

OBJECTIVES: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. PARTICIPANTS: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. RESULTS: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. CONCLUSIONS: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Impact of a major disaster on the mental health of a well-studied cohort.

IMPORTANCE: There has been growing research into the mental health consequences of major disasters. Few studies have controlled for prospectively assessed mental health. This article describes a natural experiment in which 57% of a well-studied birth cohort was exposed to a major natural disaster (the Canterbury, New Zealand, earthquakes in 2010-2011), with the remainder living outside of the earthquake area. OBJECTIVE: To examine the relationships between the extent of earthquake exposure and mental health outcomes following the earthquakes-net of adjustment for potentially confounding factors related to personal circumstances, prior mental health, and childhood family background. DESIGN, SETTING, AND PARTICIPANTS: Data were gathered from the Christchurch Health and Development Study, a 35-year longitudinal study of a birth cohort of New Zealand children (635 males and 630 females). This general community sample included 952 participants with available data on earthquake exposure and mental health outcomes at age 35 years. EXPOSURES: A composite measure of exposure to the events during and subsequent to the 4 major (Richter Scale >6.0) Canterbury earthquakes during the years 2010-2011. MAIN OUTCOMES AND MEASURES: DSM-IV symptom criteria for major depression; posttraumatic stress disorder; anxiety disorder; suicidal ideation/attempt; nicotine dependence; alcohol abuse/dependence; and illicit drug abuse/dependence. Outcomes were measured approximately 20 to 24 months after the onset of exposure to the earthquakes and were assessed using DSM-IV diagnostic criteria and measures of subclinical symptoms. RESULTS: After covariate adjustment, cohort members with high levels of exposure to the earthquakes had rates of mental disorder that were 1.4 (95% CI, 1.1-1.7) times higher than those of cohort members not exposed. This increase was due to increases in the rates of major depression; posttraumatic stress disorder; other anxiety disorders; and nicotine dependence. Similar results were found using a measure of subclinical symptoms (incidence rate ratio, 1.4; 95% CI, 1.1-1.6). Estimates of attributable fraction suggested that exposure to the Canterbury earthquakes accounted for 10.8% to 13.3% of the overall rate of mental disorder in the cohort at age 35 years. CONCLUSIONS AND RELEVANCE: Following extensive control for prospectively measured confounding factors, exposure to the Canterbury earthquakes was associated with a small to moderate increase in the risk for common mental health problems.

Moderating role of the MAOA genotype in antisocial behaviour.

BACKGROUND: Recent studies have examined gene×environment (G×E) interactions involving the monoamine oxidase A (MAOA) gene in moderating the associations between exposure to adversity and antisocial behaviour. The present study examined a novel method for assessing interactions between a single gene and multiple risk factors related to environmental and personal adversity. AIMS: To test the hypothesis that the presence of the low-activity MAOA genotype was associated with an increased response to a series of risk factors. METHOD: Participants were 399 males from the Christchurch Health and Development Study who had complete data on: (a) MAOA promoter region variable number tandem repeat genotype; (b) antisocial behaviour (criminal offending) to age 30 and convictions to age 21; and (c) maternal smoking during pregnancy, IQ, childhood maltreatment and school failure. RESULTS: Poisson regression models were fitted to three antisocial behaviour outcomes (property/violent offending ages 15-30; and convictions ages 17-21), using measures of exposure to adverse childhood circumstances. The analyses revealed consistent evidence of G x E interactions, such that those with the low-activity MAOA variant who were exposed to adversity in childhood were significantly more likely to report offending in late adolescence and early adulthood. CONCLUSIONS: The present findings add to the evidence suggesting that there is a stable G x E interaction involving MAOA, a range of adverse environmental and personal factors, and antisocial behaviour across the life course. These analyses also demonstrate the utility of using multiple environmental/personal exposures to test G×E interactions.

Risk factors for conduct disorder and oppositional/defiant disorder: evidence from a New Zealand birth cohort.

OBJECTIVE: To examine the social, family background, and individual antecedents of conduct disorder (CD) and oppositional defiant disorder (ODD), the extent to which CD and ODD symptoms were predicted by common environmental risk factors, and the extent to which the antecedents of CD and ODD accounted for the comorbidity between the two disorders. METHOD: Data were gathered from 926 members of a New Zealand longitudinal birth cohort. The outcome measures were DSM-IV symptom count measures of CD and ODD at age 14 to 16 years. Predictors measured during the period from 0 to 14 years included the following: maternal smoking during pregnancy; exposure to socioeconomic adversity; parental maladaptive behavior; childhood exposure to abuse and interparental violence; gender; cognitive ability; and affiliation with deviant peers in early adolescence. Associations between the predictors and outcome measures were modeled using structural equation modeling. RESULTS: The analyses showed that each of the predictors was significantly (p < .05) associated with CD and ODD, with the exception of gender and ODD. After model fitting, the profile of risk factors that predicted CD and ODD were largely similar. The analyses revealed that approximately 40% of the comorbidity between disorders could be accounted for by common factors. CONCLUSIONS: The data showed that CD and ODD had largely similar social and environmental antecedents. One implication of this finding is that treatment and prevention approaches that are developed for use with a particular behavior disorder may in fact reduce the incidence of both disorders.

Cigarette smoking and depression: tests of causal linkages using a longitudinal birth cohort.

BACKGROUND: Research on the comorbidity between cigarette smoking and major depression has not elucidated the pathways by which smoking is associated with depression. AIMS: To examine the causal relationships between smoking and depression via fixed-effects regression and structural equation modelling. METHOD: Data were gathered on nicotine-dependence symptoms and depressive symptoms in early adulthood using a birth cohort of over 1000 individuals. RESULTS: Adjustment for confounding factors revealed persistent significant (P<0.05) associations between nicotine-dependence symptoms and depressive symptoms. Structural equation modelling suggested that the best-fitting causal model was one in which nicotine dependence led to increased risk of depression. The findings suggest that the comorbidity between smoking and depression arises from two routes; the first involving common or correlated risk factors and the second a direct path in which smoking increases the risk of depression. CONCLUSIONS: This evidence is consistent with the conclusion that there is a cause and effect relationship between smoking and depression in which cigarette smoking increases the risk of symptoms of depression.

Cannabis use and educational achievement: findings from three Australasian cohort studies.

BACKGROUND: The associations between age of onset of cannabis use and educational achievement were examined using data from three Australasian cohort studies involving over 6000 participants. The research aims were to compare findings across studies and obtain pooled estimates of association using meta-analytic methods. METHODS: Data on age of onset of cannabis use (<15, 15-17, never before age 18) and three educational outcomes (high school completion, university enrolment, degree attainment) were common to all studies. Each study also assessed a broad range of confounding factors. RESULTS: There were significant (p<.001) associations between age of onset of cannabis use and all outcomes such that rates of attainment were highest for those who had not used cannabis by age 18 and lowest for those who first used cannabis before age 15. These findings were evident for each study and for the pooled data, and persisted after control for confounding. There was no consistent trend for cannabis use to have greater effect on the academic achievement of males but there was a significant gender by age of onset interaction for university enrolment. This interaction suggested that cannabis use by males had a greater detrimental effect on university participation than for females. Pooled estimates suggested that early use of cannabis may contribute up to 17% of the rate of failure to obtain the educational milestones of high school completion, university enrolment and degree attainment. CONCLUSIONS: Findings suggest the presence of a robust association between age of onset of cannabis use and subsequent educational achievement.

Does observer bias contribute to variations in the rate of retinopathy of prematurity between centres?

PURPOSE: We aimed to indirectly assess the contribution from observer bias to between centre variability in the incidence of acute retinopathy of prematurity (ROP). METHODS: The Australian and New Zealand Neonatal Network (ANZNN) collected data on the highest stage of acute ROP in either eye in 2286 infants born at less than 29 weeks in 1998-1999 and cared for in one of 25 neonatal intensive care units (NICUs). Chi-squared analysis was used to detect differences in the proportion of stages of ROP for each neonatal intensive care unit. These proportions were compared with those reported in two large studies of treatment for ROP. RESULTS: The incidence of acute ROP in the ANZNN cohort was 42% and the ratio of stage 1:2:3 ROP was 1.5:1.9:1. There was considerable variation in both the incidence of acute ROP and the proportions with stage 1:2:3 ROP between centres. A chi-squared test determined that the assignment of stages 1, 2 and 3/4 ROP was not independent of centre (chi(2)(48) = 165.2; P < 0.0001). Treatment of stage 3 ROP varied between 15% and 120%, indicating some eyes were treated at less than stage 3. CONCLUSION: The data are highly suggestive of observer bias contributing to the observed between centre variation in the incidence of acute ROP. In neonatal intervention studies where acute ROP is an outcome it would seem important to have an accreditation process for examining ophthalmologists, and there are similar arguments for neonatal networks which collect these data.

Childhood social disadvantage and smoking in adulthood: results of a 25-year longitudinal study.

AIM: To examine the associations between exposure to socio-economic disadvantage in childhood and smoking in adulthood. DESIGN: A 25-year longitudinal study of the health, development and adjustment of a birth cohort of 1265 New Zealand children. MEASUREMENTS: Assessments of childhood socio-economic disadvantage, smoking in adulthood and potential mediating pathways, including: parental education, family socio-economic status, family living standards and family income; smoking frequency and nicotine dependence at age 25 years; child IQ, educational achievement by age 18 years, conduct problems ages 14-16 years, parental smoking 0-16 years and peer smoking at 16 years. FINDINGS: Smoking at age 25 was correlated significantly (P < 0.0001) with increasing childhood socio-economic disadvantage. Further, indicators of childhood socio-economic disadvantage were correlated significantly (P < 0.0001) with the intervening variables of childhood intelligence, school achievement, conduct problems and exposure to parental and peer smoking; which in turn were correlated significantly (P < 0.0001) with measures of smoking at age 25. Structural equation modelling suggested that the linkages between the latent factor of childhood disadvantage and later smoking were explained largely by a series of pathways involving cognitive/educational factors, adolescent behavioural adjustment and exposure to parental and peer smoking. CONCLUSIONS: The current study suggested that smoking in adulthood is influenced by childhood socio-economic disadvantage via the mediating pathways of cognitive/educational factors, adolescent behaviour and parental and peer smoking.