Although individual genetic markers from genome-wide association studies (GWAS) usually explain limited heritability especially in psychiatric traits, polygenic scores can be a better way to summarise genetic effects of a large number of markers that do not individually achieve geneome-wide significance. (Dudbridge, 2013). This approach has been applied succesfully to schizophrenia (Purcell et al, 2009) and bipolar disorder (Hamshere et al, 2011).

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. Traits of ADHD are present in family members of those with the conditions, as well as in the general population. Learning disabilities are common in ADHD with up to 40% of children with a diagnosis of ADHD presenting with them (Willcutt et al, 2000). In addition, neurocognitive deficits are seen in ADHD with executive function being the primary deficit (Willcutt et al, 2000). Given the attention problems that children with ADHD face, it is expected that their school performance will be affected.

Our hypothesis is that polygenic risk scores based on a clinical sample of ADHD will predict educational attainment and IQ in children from the general polulation.

Polygenic risk scores were calcualted on ALSPAC children using a GWAS of 727 ADHD patients and 5,081 controls (Stergiakouli et al, 2012) as a discovery sample (project B1342) and were provided by colleagues in Cardiff.

Aims of proposal:

To test if polygenic risk scores predict school performance in ALSPAC children using SATS school scores. We are expecting that higher polygenic scores for ADHD will be associated with worse performance in school.

To test if polygenic risk scores predict IQ in ALSPAC children using the WASI IQ score from Focus@3 clinic. We are expecting that higher polygenic scores for ADHD will be associated with lower IQ scores at age 15.

The training sample GWAS from Cardiff did not identify any genome-wide significant hits but it did find that 13 biological pathways enriched for SNP association significantly overlapped with those enriched for rare CNVs. These included cholesterol-related pathways. At the level of individual genes, CHRNA7, which encodes a nicotinic receptor subunit previously implicated in neuropsychiatric disorders, was affected by six large duplications in case subjects (none in comparison subjects) (Stergiakouli et al, 2012). Our hypothesis is that polygenic risk scores based on genetic variants from the GWAS mentioned above could predict obesity and smoking behaviour in the general population.

Aims of proposal:

To test if polygenic risk scores predict BMI at ages 7, 9 and 15 and lipid levels at age 9.

To test if polygenic risk scores predict smoking behaviour at age 15.

Aims

The aims of this project are to assess the long-term effects of adolescent cannabis use on cognitive functioning. Previous research has suggested heavy cannabis use in the teenage years may lead to persistent neuropsychological deficits; however much of the research to date has been cross-sectional and therefore unable to assess whether pre-exposure group differences are driving the association. A recent longitudinal study found chronic heavy cannabis use was associated with a decline in IQ in those with adolescent-onset cannabis use, but not in those with adult-onset use (Meier et al, 2012). However this study had a number of important limitations, including small group sizes and failure to account for a number of potential confounding variables adequately. The present study will address these issues with an independent, larger sample, and assess other factors that may contribute to the relationship.

Research Questions

1. Is heavy cannabis use in adolescence associated with a decline in IQ?

2. Does the neuropsychological functioning of different cannabis-exposure groups differ in childhood, i.e. before onset of drug use? Do the exposure groups differ in other ways (e.g. early environment, socioeconomic status) that might influence neuropsychological functioning?

3. Does adolescent cannabis use affect cognitive function once pre-exposure functioning and other potential confounders (e.g. mental illness or socioeconomic status) have been accounted for? If so what is the size of this effect, and is this also reflected in academic acheivement?

4. Are any deficits seen globally across all neuropsychological functioning, or are they specific to certain domains (e.g. attention or decision making)?

Exposure variables:

1. Cannabis use. This measure will be defined according to lifetime reported usage between ages 13-18 years.

2. Cannabis dependence. This measure will be defined according to criteria for cannabis dependence between ages 16-18 years.

Outcome variables:

1. IQ change from childhood to adolescence. This outcome will be defined based on performance on IQ assessments completed at ages 8 and 16.

2. Neuropsychological functioning. This outcome will be defined by performance on cognitive tasks completed between ages 16-18 years.

3. Academic acheivement. This outcome will be defined by performance on academic assessments completed at school year 11 (Key Stage 4).

Confounding variables:

1. Pre-exposure neuropsychological functioning. Pre-existing differences or deficits in cognitive and academic ability are likely to be related to post-exposure functioning

2. Pre-exposure academic performance. Problems at school in childhood may influence cognitive development and may also be related to the initiation of cannabis use

3. Childhood temperament and behaviour. Childhood traits may influence cognitive development and may also be related to initiation of cannabis use

4. Mental illness (including depression, psychosis and conduct disorder) will likely influence neuropsychological functioning and task performance

5. Sex, socioeconomic status (e.g. parental years of education) and early environment/ parental factors (e.g. parental IQ or drug use) will likely influence neuropsychological functioning

6. Other substance use and dependence (including alcohol and tobacco) may influence neuropsychological functioning

7. Recent cannabis exposure at testing will likely affect performance on neuropsychological assessment due to acute (use in the past 24 hours) and residual (use in the past month) effects of the drug

Reference

Meier, M.H., Caspi, A., Ambler, A., Harrington, H., Houts, R., Keefe, R. S. E., McDonald, K., Ward, A., Poulton, R., & Moffitt, T. E. (2012) Persistent cannabis users show neuropsychological decline from childhood to midlife. PNAS, 109, 1-8.

This proposal will address the need to better understand the interplay between behavioural and biological mechanisms in human development. It will make substantial contributions to our theoretical understanding of social and cognitive development, social behaviour, and their impact on health and behaviour in childhood, adolescence and early adulthood, integrating recent developments in epigenetics. It will develop the empirical knowledge base in these areas, in order to support the development of novel interventions, and create an international hub linked to existing major research groupings.

Intrapersonal, interpersonal and environmental influences (such as family environment, early adversity, and socioeconomic position) at different stages of the life course are critical to the development of behaviour. These influences need to be understood in order to develop and optimise interventions to improve health and wellbeing. However, knowledge of the behavioural and psychological mechanisms of behavioural control, their development through infancy, adolescence and early adulthood, and their relationship with social behaviour, health and wellbeing, remain poorly integrated, and are rarely (if ever) investigated within a single data set. We propose a cohesive programme of research intended to provide a comprehensive understanding of the relationship between cognition, social behaviour, and impulsivity and risk taking. This will be allied to a life course perspective, to understand the role of social and environmental influences at every stage of development into early adulthood.

The Avon Longitudinal Study of Parents and Children (ALSPAC) forms the core resource on which this proposal is structured, utilising the wide range of phenotypic and environmental measures available, in addition to biological samples, genetic and epigenetic information and linkage to health and administrative records. This proposal is a collaborative project across the Universities of Bath, Bristol, Cardiff and Exeter, and will be supported by a wider network of national and international collaborators. It will be structured into three main workstreams, corresponding to our three main aims.

Aim 1: Understand the cognitive precursors (e.g., attentional and perceptual processes) of social behaviour, and health and wellbeing.

Aim 2: Understand the developmental pathways, trajectories and mechanisms associated with social behaviour (in particular sexual behaviour and aggressive behaviour).

Aim 3: Understand social, cognitive and environmental influences on impulsivity and high-risk behaviours, and subsequent health and wellbeing.

Workstream 1 (Social and Cognitive Development): This work will focus on the cognitive precursors of social behaviour, and health and wellbeing. There is growing interest in the extent to which domain-general processes, particularly attentional and perceptual processes, play a role in the development of social cognition and theory of mind. In addition, social compliance, particularly in children, may depend on individuals' ability to adopt, maintain, and execute appropriate goals. As a consequence, executive control functions, including working memory, constrain the manifestation of social behaviour, including the impact of social context, parenting and imitation. However, a central problem that has limited progress in this area is the poor specification of executive control, particularly in children. Until recently, working definitions of the construct have relied on a loose collection of putative executive functions. Structural equation modelling has since provided frameworks for organizing these functions, with a focus on updating, inhibition, and shifting, but these still lack a clear theoretical basis. We will therefore examine the development of executive control in children using a principled approach that sets these candidate functions in a theoretical context. This follows directly from two claims: 1) executive function represents the individual's ability to maintain task goals (updating) and to use these to prevent them from acting inappropriately in response to external stimuli (inhibition), and 2) executive control has a temporal aspect that is not independent of previous experience (shifting). We have the expertise to employ precise measures of these functions and, crucially, manipulate them orthogonally to properly test their interplay. Armed with this suite of novel but theoretically-motivated tasks, the relationship between executive control, measures of attention/perception, measures of social context and parenting, and social behaviour will be investigated. We will explore the relationship of executive function in early life and later trajectories of social and cognitive development, social behaviour, and impulsivity and high-risk behaviour. This will be done in a new longitudinal study across three time points over three years. We will also explore atypical groups based on measures of autism spectrum disorder and attention deficit hyperactivity disorder, the developmental trajectories of these traits over time in ALSPAC, and use targeted recall studies of ALSPAC participants who score at the extreme of measures of executive function to investigate cognitive mechanisms in more detail, using both behavioural and fMRI methods.

Workstream 2 (Social Behaviour): This work will examine the developmental pathways, trajectories and psychological mechanisms associated with outcomes in two aspects of social behaviour that have significant societal impacts: sexual behaviour and aggressive behaviour. Life history theory provides a meta-theory for the coherent study of sociosexual and aggressive behaviour at functional, ontogenetic and mechanistic levels. It proposes that timing of important events across the lifespan, and the strategies employed to achieve such goals, are determined by flexible mechanisms that function to increase reproductive success in response to environmental conditions. Human behavioural ecologists have successfully applied this theoretical approach to societally-important issues such age of first reproduction, family size, and parental investment as a function of factors such as socio-economic status and childhood social experiences, and researchers in other disciplines have investigated the neural, endocrinological and psychological mechanisms underlying such behaviour. We will integrate work across these levels of explanation (function, ontogeny, and mechanism), with a particular focus on the development of emotional processing strategies, which play an important role in sexual and aggressive behaviour. Our underlying theory is that biases in emotional processing often reflect adaptive calibration of socio-cognitive mechanisms to the current environment. For example, links between hostile childhood environments and later aggressive behaviour are well established, and may be functional: when exposed to chronically hostile environments in development, aggression may be an adaptive, rather than a maladaptive, strategy in many cases. We will use the ALSPAC cohort to identify emotion processing strategies that mediate the relationships between childhood environments and social outcomes in adolescence and young adulthood. This will allow us to examine trajectory and development of social behaviours, investigating the role of genetic, epigenetic and social/environmental factors (including physical trauma such as head injury) on development. We will use these analyses to design targeted recall studies in the ALSPAC cohort, to investigate underlying psychological mechanisms using both behavioural and fMRI methods.

Workstream 3 (Health and Wellbeing): This work will examine the relationship between social and cognitive development, social behaviour and health behaviour in adolescence and early adulthood. Psychological models of health behaviour have traditionally focused on explicit decisions arising from cognitive appraisal processes. More recently, dual-process models have emerged which integrate evidence that automatic, impulsive processes also play an important (and perhaps dominant) role. Critically, a constellation of high-risk behaviours (e.g., aggressive behaviour, sexual behaviour, substance use) frequently co-occur, and many adolescents engage in these behaviours at levels harmful to health and wellbeing. It is therefore logical to focus on determinants of these multiple risk behaviours, as this may provide single targets for intervention with the potential for broad impact. Current dual-process models argue that interacting, neural systems control decision making, with an impulsive system focused on immediate consequences and a reflective system focused on future prospects. The reflective system governs the impulsive system; however, there are individual differences in the extent to which this is the case, and this is related to executive function. Therefore, factors which influence cognitive and social development in childhood may in turn influence impulsive and high-risk behaviours in adolescence and early adulthood, both directly (via individual differences in executive function) and indirectly (via exposure to peer groups and other environmental risks). We will explore the relationship between cognitive and social development in early life, and subsequent impulsive and high-risk behaviour in adolescence and early adulthood. We will identify the impact of environmental exposures at multiple time points (e.g., tobacco exposure in utero, in childhood in the home, in adolescence in the home and via peer groups) on subsequent impulsive and high-risk behaviours, and explore the mechanistic relationships between these variables using targeted recall methods to enable more intensive characterisation of relevant constructs, epigenetic markers of exposure, and Mendelian randomisation where possible.

AIMS:

Is the presence of parent-reported "choosy" or "difficult to feed" behavior in children associated with GI symptoms (gastroenteritis, diarrhoea, vomiting, stomach ache and stool type)?

Is the presence of parent-reported "choosy" or "difficult to feed" behavior in children associated with alterations to either parent or child quality of life?

Is the presence of parent-reported "choosy" or "difficult to feed" behaviour in children associated with differences in the child's dietary intake at 1.5, 3.5 and 10 years or later food preference (e.g. large intakes of milk/dairy foods or sweet foods)?

Is early life dietary intake/ timing of weaning or complementary foods (from Infant FFQs at 6 & 15 months of age) associated with eating behaviors (choosiness or difficulty feeding)?

Is early life dietary intake/ timing of weaning or complementary foods (from Infant FFQs at 6 & 15 months of age) associated with reports of child GI symptoms (gastroenteritis, diarrhoea, vomiting, stomach ache and stool type)?

Is early life dietary intake/ timing of weaning or complementary foods (from Infant FFQs at 6 & 15 months of age) associated with differences in the child's dietary intake at 1.5, 3.5 and 10 years or later food preference (e.g. large intakes of milk/dairy foods or sweet foods)?

Is maternal dietary intake during pregnancy associated with eating behaviors (choosiness or difficulty feeding)?

Is maternal dietary intake during pregnancy associated with reports of child GI symptoms (gastroenteritis, diarrhoea, vomiting, stomach ache and stool type)?

Is maternal dietary intake during pregnancy associated with differences in the child's dietary intake at 1.5, 3.5 and 10 years or later food preference (large intakes of milk/dairy foods or sweet foods)?

There is evidence that both particular genes (heritability as high as 60%) and particular environments contribute to vulnerability to subsequent alcohol abuse and dependence [Mcgue, 1999; Enoch and Goldman, 2001; Lesch 2005]. However, there is relatively little data on gene-environment interactions in the aetiology of alcohol use disorders (AUDs) [van der Zwaluw and Engels, 2009]. Further, little is known about the role of internalising behaviour in mediating the relationship between genes, environments and subsequent AUDs.

The Avon Longitudinal Study of Parents and Children (ALSPAC) provide a unique opportunity to try and determine the relationship between genes and environments in AUDs, through the mediation of internalising behaviour. First, ALSPAC includes data on genetic variants and on adverse environments (e.g. stressful life events (SLEs)). Second, ALSPAC includes comprehensive data on internalising behaviour experienced during childhood.

Heavy alcohol use is positively associated with the experience of environmental stressors such as job, health-related, social and legal stress [Dawson et al., 2005]. In turn, the behavioural response to stress is mediated by corticotrophin-releasing factor (CRF) [Arborelius et al., 1999; Binder and Nemeroff, 2010]. Studies involving animal models have shown that polymorphisms within the CRF receptor gene (CRHR1), together with the experience of environmental stress factors, result in greater alcohol consumption [Sillaber et al., 2001; Hansson et al., 2006]. Similarly, in humans, polymorphisms in the CRHR1 gene interact with negative life events to predict heavy alcohol use [Treutlein et al., 2006; Blomeyer et al., 2008]. Besides the CRHR1 gene, the CRF pathway consists of the following genes: POMC, UCN, CRH, CRHR2, UCN3 and UCN2 [PharmGkB. Date accessed: 13 March 2013]. These genes are relatively unexplored in terms of vulnerability to alcohol dependence.

It is often argued that AUDs are characterised by externalising behaviour [Kumpulainen, 2000; Englund et al., 2008]. Findings regarding the link between behavioural inhibition/internalizing symptoms and AUDs are less emphasised in the literature, although a few studies have shown that internalising symptoms, such as anxiety and depression, are associated with alcohol use [Loeber et al., 1999; Fite et al., 2006]. CRF has also been shown to play a role in internalising behaviours; indeed polymorphisms within CRHR1 have shown to have a significant association with anxious temperament and have an influence on the metabolic activity of local brain regions in rhesus macaques [Rogers et al., 2012]. There has been little work, however, on the relationship between variants in the CRF pathway and internalising behaviour in humans.

Methodology

1) Select variants from the genes involved in the CRF pathway based on a systematic review of the literature.

2) Include genotype in the models as a (a) quasi-continuous, (b) time-invariant predictor of latent continuous and/or (c) categorical variable

i. Test for association with the extended alcohol use phenotype measured by the 10-item Alcohol Use Disorders Identification Test (AUDIT) administered at 16 years of age or later [Heron et al., 2012].

3) Identify mediating pathways by which genes confer susceptibility

i. Hypothesized that CRF genes will be likely to confer risk via internalising behaviour evident in early childhood. Internalising behaviour will be measured by the parent-rated, emotional subscale of the Strength and Difficulties Questionnaire (SDQ), administered at 7 years of age or older as described by Araya et al. (2008) and Evans et al. (2008).

ii. Hypothesized that CRF genes will be related directly to alcohol use and risk pathways in adolescence that emerge concomitantly with AU and not involved in pathways with origins in childhood

4) Test GxE with environments previously shown to moderate genetic risk. Environmental factors such as SLEs will be measured using Section D of the parent-rated questionnaire "My Son's/Daughter's Health and Behaviour-42 months". SLEs will also be assessed by the "Life Events" questionnaire completed by the Mother of the "child" at 18, 30, 42 and 57 months as well as 5, 6 and 8 years and completed by the "child" at 16 years of age.

i. Regressing outcome variables onto (a) genotype (b) an environment, and (3) and interaction term reflecting the product of genotype and environment.

We hypothesize that the enhanced asthma risk following infant RSV exposure is due to two non-mutually exclusive factors: (1) a genetic predisposition common to both diseases and (2) infant RSV infection acting as a causal agent in asthma development. We will use genetic epidemiological methods to determine the extent to which infant RSV infection plays a causal role in the development of asthma or if it merely serves as a marker of shared genetic risk with asthma. This study leverages multiple existing US based cohorts, including the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE; Hartert, PI), the Tennessee Children's Respiratory Initiative (TCRI; Hartert, PI), RSV Bronchiolitis in Early Life (RBEL I and II; Castro, PI), and Childhood Origins of Asthma (COAST; Lemanske, PI). This revised grant improves power for genetic studies and builds infrastructure to understand infant RSV infection and its respiratory sequelae by collaborating with longitudinal cohorts that have well-characterized respiratory infections in infants during the first year of life followed through to early childhood wheezing/asthma outcomes. We will first identify the genes associated with response to RSV infection (Aim 1) and then determine the genetic bases of shared RSV infection and recurrent wheezing/ early asthma susceptibility (Aim 2). This would be the first GWAS of RSV infection in infancy and its respiratory sequelae of recurrent wheezing/asthma.

We would like to use existing GWAS data from ALSPAC for replication of our primary findings.

Specific Aim 1a:

1a) We will identify the genetic determinants of the severity of RSV infection in the first year of life among ~2000 infants from multiple US cohorts with confirmed RSV exposure or infection. For GWAS genotyping, we will use the Illumina HumanCore + Exome BeadChip in European-Americans (EAs) and the Illumina Omni 2.5M + Exome BeadChip in African-Americans (AAs) and Hispanic-Americans (HAs).

Specific Aim 1b) We will perform a pathway analysis of genome-wide data that addresses limitations of SNP analyses to identify genes or pathways that are associated with severity of RSV infection during infancy.

Specific Aim 2: We will identify the specific genetic variants that lead to the shared genetic risk of severity of RSV infection and early childhood recurrent wheezing/asthma.

This proposed collaboration will address an important gap in understanding how severe infant RSV infection increases the risk of recurrent wheezing/asthma. The results will provide novel insights into both the timing and mechanism for developing primary prevention strategies.

Based on two papers from the ALSPAC cohort, both involving collaborator John Henderson, there are 284 infants hospitalized with infant bronchiolitis. The ALSPAC cohort has well characterized wheezing and asthma outcomes. Using this existing data, we would like to replicate our SNPs predicting severe infant bronchiolitis, measured as hospitalization (y/n). We would also like to replicate SNPs that examine risk of wheezing/asthma after hospitalization for bronchiolitis. We propose in Specific Aim 1b and in exploratory analyses for asthma outcomes to conduct pathway analyses. We would like to use existing ALSPAC data to conduct a replication of our pathway analysis. This will entail the analysis of existing GWAS data.

If the sample size for hospitalization with bronchiolitis followed to to wheezing / asthma outcomes includes enough children with DNA available, we would like to consider using your genetics lab for replication of 480 SNPS from Aim 1 and 480 SNPs from Aim 2 using cases a set of matched controls. At this point we do not know whether our primary SNPs will exist in your data set. We also do not know whether there will be enough children from the case group with DNA.

AIMS

This study aims to investigate the affect of iodine and sodium status throughout pregnancy on outcome of the offspring.

HYPOTHESIS

Iodine is required for the production of thyroid hormones which have a role in brain and neurological development during gestation and early life. The mother is an important source of thyroid hormones to the developing fetus particularly before the fetus is able to produce its own. Mild to moderate maternal iodine deficiency has been associated with a reduction in IQ and psychomotor development in the offspring and has also been linked to the development of ADHD. Excessively high or low intake of sodium throughout pregnancy can have adverse effects on both the mother and the offspring and therefore maternal sodium levels will also be analysed in the urine. Measuring iodine and sodium levels in maternal urine throughout pregnancy and analysing against offspring outcome will identify the most influential period of development on which iodine and sodium have an affect.

EXPOSURE VARIABLE

All maternal urine samples from each trimester

OUTCOME VARIABLE

Iodine, sodium and creatinine levels. Creatinine will be analysed to correct for urine volume.

CONFOUNDING VARIABLES

maternal age at delivery, mother's parenting score, HOME score, family adversity index, life-event score, intakes of omega-3 fatty acids and iron

child factors

sex, birthweight, preterm birth, breastfeeding, and ethnic origin

maternal factors

smoking status, alcohol intake, parity, maternal depression since birth and use of fish-oil supplements during pregnancy

markers of socioeconomic status

maternal and paternal education, housing status and crowding

This study aims to:

a) Independently assess the predictability of early social experiences [family, school and peers] upon the initiation and progression of substance use in late adolescence, and examine if they vary in importance according to different substances [alcohol, cannabis, smoking] and/or level of use [experimental, occasional, regular].

b) Examine the extent to which family relations and/or school experiences in childhood and substance use in late adolescence are mediated by peer's substance use in early adolescence.

c) Create two models of substance use: one to test whether peer use is moderating the effect of parent-child relationships upon substance use in late adolescence; and the other to test whether peer use is moderating the effect of school connectedness on substance use in late adolescence.

Background:

Alcohol use disorders (AUDs) are highly prevalent, affecting 3.6% of the global population (Rehm, Mathers & Popova et al., 2009). AUDs impact on the physical (liver disease, brain damage and injuries) as well as psychological well-being of the affected individual. Furthermore, AUDs have a considerable impact on the affected individual's family, larger social circle and society as a whole. There is a considerable genetic component to AUDs with heritability estimates of ~50-60% (van den Bree, Johnson eta, 1998). As many as 15% of children report living with an alcoholic parent (US data reported by Grant, 2000) while 43% of Children of Alcoholic parents (CoAs) will themselves develop an AUD in adulthood (Grant, 2000). It is therefore important to understand the developmental pathways of alcohol use/ misuse in this high-risk population.

Children of Alcoholics:

CoAs have been consistently reported to have poorer academic achievement than children of non-alcoholic parents (non-CoAs) (e.g. Puttler, Zucker, Fitzgerald and Bingham, 1998; Diaz, Gual & Garcia et al., 2008). However, the evidence regarding impaired performance on cognitive assessments (e.g. WASI/WISC) is less clear, with some studies reporting worse full-scale, verbal and performance IQ in CoAs (e.g. Diaz, Gual & Garcia et al., 2008) (Yang & Kramer, 2012), while others report no difference (e.g. Kultur, Unal & Ozusta, 2006). There have been no studies based on a large scale longitudinal population-based sample.

One of the most consistently reported differences between children with and without alcoholic parents is increased problem behaviours. These include externalising and antisocial behaviours, as well as internalising and hyperactive behaviours. Externalising and antisocial behaviours have been reported in children with alcoholic parents from a very young age, even including infancy (Edwards, Eiden, Colder & Leonard, 2006). These behaviours then appear to persist throughout development into adolescence (Hussong, Huang & Curran et al., 2010). Internalising behaviours, such as negative affect and anxiety are less reliable reported. There have been some positive results in early childhood (Haugland, 2003), but the majority of studies have reported that internalising behaviours become more common in children with alcoholic parents during adolescence (Hussong, Cai & Curran et al., 2008). This increase during adolescence may be related to the onset of the child's own alcohol use.

There is some evidence that suggests that maternal and paternal alcohol use can have differential effects on offspring (Connell & Goodman, 2002) and that offspring gender can influence the impact of parental alcohol use (Eisenberg, Haugen & Spinrad et al., 2010). Social factors, such as parental-offspring relationships and peers, can also influence the effect of parental alcohol use on the offspring (Stice & Barrera, 1995).

Current proposed study:

There is currently an absence of large population-based longitudinal studies which examine the associations between parental alcohol problem use and offspring behaviour. While there have been a number of small-scale longitudinal studies using high-risk populations (e.g. Chassin, Rogosch & Barrera, 1991; Eiden, Edwards, Colder & Leonard, 2009) and some larger population-based comparative studies (e.g. Yang & Kramer, 2012), there have been no studies which have the breadth of information available in the ALSPAC data set.

We propose to use already collected ALSPAC data to address the important issue of parental alcoholism. We will compare with and without alcoholic parents in the areas of cognition, behaviour, psychiatric problems and substance use. Additional analysis will be used to see if offspring's own alcohol use contributes to any differences we find and to see if parent or offspring gender and offspring's peer group also have an impact.

Aims:

1. Conduct comparisons between CoAs and nonCoAs at an early age (i.e. age 8), before alcohol use initiation, on relevant indices reported in the literature, including behaviour, academic performance and cognition, social factors (family and peer relations), and mental health problems.

Sub aims: examine any evidence for gender-specific effects (i.e., parent or offspring)

2. Conduct similar comparisons at later ages (i.e. 8-15), when participants are increasingly starting to use alcohol. Here comparisons will also include alcohol and other substance use at different ages.

3. Examine the longitudinal alcohol use/ misuse trajectories for CoAs and non-CoAs and to what extent specific covariates (see above) play a role in any differences.

Analyses:

Analysis 1 and 2. ANOVAs, chi-square tests, or regressions where CoA (yes/ no) is the dependent variable.

Analysis 3. Trajectories already exist. Each individual in the sample has been assigned a probability of belonging to different categories based on repeated measures of alcohol use collected at different ages. We will plot the trajectories for the two groups. We will conduct regression-based analysis to determine whether CoAs are more likely to belong to certain alcohol trajectories compared to non-CoAs, before and after adjustment for covariates.

References:

Chassin, L, Rogosch, F, & Barrera, M. (1991). Substance use and symptomatology among adolescent children of alcoholics. Journal of abnormal psychology 100(4), 449-463.

Connell, A.M., & Goodman, S.H (2002). The Association Between Psychopathology in Fathers Versus Mothers and Children's Internalizing and Externalizing Behaviour Problems: A Meta-Analysis. Psychological Bulletin, 128 (5), 746-773.

Diaz, R., Gual, A., Garcia, M., Arnau, J., Pascual, F., Canuelo, B., & Garbayo, I. (2008). Children of alcoholics in Spain: From risk to pathology. Social psychiatry and psychiatric epidemiology, 43(1), 1-10.

Edwards, E. P., Eiden, R. D., Colder, C., & Leonard, K. E. (2006). The Development of Aggression in 18 to 48 Month Old Children of Alcoholic Parents. Journal of abnormal child psychology, 34(3), 409-423.

Eiden, R. D., Colder, C., Edwards, E. P., & Leonard, K. E. (2009). A longitudinal study of social competence among children of alcoholic and nonalcoholic parents: Role of parental psychopathology, parental warmth, and self-regulation. Psychology of addictive behaviors, 23(1), 36-46.

Grant, B.F. (2000). Estimates of US Children Exposed to Alcohol Abuse and Dependence in the Family. American Journal of Public Health, 90 (1), 112-115.

Haugland, B. S. M. (2003). Paternal alcohol abuse: Relationship between child adjustment, parental characteristics, and family functioning. Child psychiatry and human development 34(2), 127-146.

Heron, J., Macleod, J., Munafo, M. R., Melotti, R., Lewis, G., Tilling, K., & Hickman, M. (2012). Patterns of alcohol use in early adolescence predict problem use at age 16. Alcohol and alcoholism, 47(2), 169-177.

Hussong, A. M., Cai, L., Curran, P. J., Flora, D. B., Chassin, L. A., & Zucker, R. A. (2008). Disaggregating the distal, proximal, and time-varying effects of parent alcoholism on children's internalizing symptoms. Journal of abnormal child psychology 36(3), 335-346.

Hussong, A. M., Huang, W., Curran, P. J., Chassin, L., & Zucker, R. A. (2010). Parent alcoholism impacts the severity and timing of children's externalizing symptoms. Journal of abnormal child psychology, 38(3), 367-380.

Kultur, S. E. C., Unal, M. F., & Ozusta, S. (2006). Psychopathology in children of alcoholic fathers. Turk Psikiyatri Dergisi, 17(1), 3-11.

Puttler, L. I., Zucker, R. A., Fitzgerald, H. E., & Bingham, C. R. (1998). Behavioral outcomes among children of alcoholics during the early and middle childhood years: Familial subtype variations. Alcoholism: clinical and experimental research, 22(9), 1962-1972.

Rehm, J., Mathers, C., Popova, S., Thavorncharoensap, M., Teerawattananon,Y., & Patra, J. (2009). Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet, 373, 2223-2233.

Stice, E., & Barrera, M. (1995). A longitudinal examination of the reciprocal relations between perceived parenting and adolescents' substance use and externalizing behaviours. Developmental psychology, 31(2), 322-334.

van den Bree, M., Johnson, E. O., Neale, M. C., & Pickens, R. W. (1998). Genetic and environmental influences on drug use and abuse/dependence in male and female twins. Drug and alcohol dependence, 52(3), 231-241.

Yang, S., & Kramer, M. S. (2012). Paternal alcohol consumption, family transition and child development in a former Soviet country. International Journal of Epidemiology, 41(4), 1086-1096.