Aims and Hypothesis

During the production of lymphoblastoid cell lines for the ALSPAC cohort there has been circumstantial evidence that lymphocytes from some individuals are harder to transform with Epstein Barr Virus than others. Also there is variation in the growth rate of different cultures. The ALSPAC laboratory has collected data on the rate of transformation and rate of growth of cultures once transformed.

We would like to run a GWAS analysis of the cell line characteristics to see if there is a genetic association with transformation success or growth rate of the cultures. In particular we will look to see if genes that have been identified as host genes associated with cancers caused by Epstein Barr Virus are also associted with transformation efficiency. (HLA-A has been shown to be associated with risk of EBV-related Hodgkin lymphoma (Hjalgrim, et al., 2009, Urayama, et al., 2011) and Nasopharyngeal carcinoma (Tse, et al., 2009).

In addition there are phenotypes which could affect the transformation success, for example a recent or past infection with EBV. There are also some reports which suggest that blood pressure ia associated with different cell line growth rates. Therefore we will look to see if there is any association between the cell line characteristics and the infection history, blood pressure and smoking data of the participants the cell lines were obtained from.

Exposure Variables

Smoking, blood pressure and infection history

Outcome Variables

Transformation success rate and growth rate of established cultures

Confounding Variables

Cell counts of original samples, time to processing, original blood volume, age of participant

Karen Ho, ALSPAC cell line RA will provide all the cell line data which can also be incorporated into the main ALSPAC resource. George McMahon has agreed to carry out the GWAS analysis and assist with general statistical analysis.

Any findings could potentially be replicated using data obtained from 1958 birth cohort cell lines subject to approval from the 1958 birth cohort access committee.

The aim of our study is to study different aspects of sleep in relation to cardiovascular risk factors. The ALSPAC data has a uniquely wide range of sleep variables collected from birth and detailed information on cardiovascular function at aldolescence. Since the information on sleep was collected at a very young age, the main limiation of previous studies, i.e. reverse causation due to an underlying vascular disorder, is most likely to be avoided.

Background: Research has established that the media can influence suicidal behaviour [5]. This may occur through processes of contagion, imitation and transmission of methods. The Internet is a relatively new medium that is transforming the environment for the communication of information about suicide. As well as providing an outlet for traditional sources of media such as news reports, which are known to influence suicidal behaviour, it also poses additional and unique challenges. It allows instantaneous, repeated and global sharing of a broad array of information, including detailed 'how to' information about suicide methods. It also enables creation and interactive exchange of user-generated content through social media platforms, such as chat rooms, blogging, video sites and social networking sites [6]. Information may derive from individuals as well as institutions, meaning that new and anonymous voices can contribute, uncensored to dialogue about suicide [1], and create pro-suicide 'extreme communities' [7] which may encourage suicide as a response to difficulties. Internet use may therefore increase access to suicide [8] both physically, though transmission of methods, and cognitively by endorsing this as a culturally available response to distress. The Internet and social media are fundamental to the way that many people share information, opinions and ideas. There are over two billion Internet users worldwide and use is most prevalent amongst young adults (aged 16-24years) [1].

Concern about the potential for the Internet to cause suicide is at an all time high with mounting cases of internet-related suicide reported in the popular and academic press (e.g. [9] [10] [11]). These provide examples of individuals using suicide methods discovered online, accessing drugs for overdose from unregulated online pharmacies, and being encouraged to attempt suicide through participation in chat room discussions. Social networking has been implicated in recent suicide clusters such as Bridgend. While such examples demonstrate that the Internet can contribute to suicidal behaviour in a range of ways, much of this literature in this field is impressionistic. There is little systematic empirical evidence. Studies of Internet content reinforce the notion that detailed information about suicide methods can be accessed easily [12] [13], however, these studies cannot inform about actual user behaviour in accessing these sites or how such information is interpreted. Prevalence estimates of suicide-related internet use are currently lacking. Existing studies of users tend to be based on self-selecting samples responding to online adverts and questionnaires [2] [3]. While furthering concerns about possible harmful effects of the Internet, these studies also draw attention to the possibility that for some individuals, the Internet provides a constructive and supportive environment for dealing with suicidal feelings. This raises the prospect of exploiting the Internet for prevention purposes but to achieve this requires understanding of what users seek online and what material will engage them. Detailed empirical study examining how, when and for what purpose the internet is used by individuals with suicidal feelings and how this shapes suicidal behaviour is now required to inform attempts to both restrict harmful use and to capitalise on the Internet's potential to offer population level suicide prevention.

Aims: To provide detailed empirical evidence about the use of the Internet for suicide-related purposes by young adults and how this influences suicidal feelings and behaviour.

Design: This project will involve using data from the section on deliberate self-harm in the forthcoming ALSPAC 20 years questionnaire, including questions about suicide-related Internet use formulated by the applicants (LB and DG). The data will be used to conduct quantitative analysis and derive a purposive sample for further qualitative data collection. This project forms part of a larger application, which will also explore Internet amongst other groups.

1. Quantitative analysis

This is a descriptive, exploratory study and so there are not specifc hypotheses. The main objectives will be to:

1) provide prevalence estimates of suicide-related internet use amongst young adults, including those who self-harm and/ or experience suicidal thoughts

2) to investigate socio-demographic and clinical characteristics associated with use.

Exposure variables: deliberate self-harm, suicidal thoughts

The outcome variable will be whether or not the Internet has been used for suicide-related purposes.

Data analysis: Descriptive statistics, bivariate analysis and logistic regression techniques will be used to:

* Estimate the prevalence of suicide-related Internet use by young adults

* Describe the nature of Internet use including: frequency; material accessed; use of search engines; engagement with chat room and other discussion forums; use of support/ prevention sites.

* Investigate the association between Internet use and socio-demographic characteristics; self-harm (including frequency, method and intent); suicidal thoughts; and formal help-seeking behaviour.

After considering total prevalence and patterns of Internet use amongst all responders, analysis will focus on 3 sub-groups, individuals reporting (past year): 1) self-harm; 2) self-harm with suicidal intent; 3) suicidal thoughts. Results will be presented as percentages or odds ratios with 95% confidence intervals and p-values. Data analysis will be performed using STATA (v12).

2. Qualitative interviews

The main objectives will be to:

1) derive in-depth qualitative accounts of Internet use exploring: how, why and when the Internet is accessed; the material that is viewed and how this is interpreted; how use changes over time; and how use shapes suicidal behaviour.

2) investigate how supportive/ preventative web material is evaluated by Internet users who experience suicidal thoughts/ behaviour.

Sampling: Respondents who report recent (past year) self-harm/ suicidal thoughts and that they have used the Internet for suicide-related purposes in the 20 years questionnaire will form a sampling frame for in-depth qualitative interviews. We will seek to use maximum variation sampling to obtain a diverse sample in terms of gender, nature of self-reported self-harm and suicidal thoughts (e.g. frequency, method used, suicidal intent), and nature of Internet use. In particular, we will seek to include participants who report visiting support and prevention sites as well as those visiting pro-suicide sites. The aim will be to conduct around 25 interviews though exact sample size will be determined according to the number of participants required to achieve a consistent and refined understanding of the main themes across a diverse group. Based on our previous experience of qualitative research in this area, we anticipate that some respondents will yield extremely rich and complex data as multiple episodes of suicidal behaviour and Internet use are likely to be presented within single cases. Two of our previous studies with mentally distressed young adults and near-fatal suicide attempters have been based on sample sizes of 23 [14] and 22 [15] participants.

Data collection and analysis: ALSPAC assistance will be required to obtain a sample only. All further data collection will be undertaken independently by the research team headed by Biddle et al. Interviews will be in-depth and semi-structured. They will be conducted within the interpretive tradition[16] and in keeping with an ethnographic grounded theory approach [17]. Detailed narrative accounts of Internet use in relation to suicidal feelings and behaviour will be sought, focusing on:

* How (including search strategies), why and when (for example, along the suicidal pathway) the Internet is accessed;

* how Internet use evolves over time;

* the material that is viewed (including types of site and participation in chat rooms) and the meanings/ evaluations attached to this;

* the impact of use on suicidal feelings and behaviour;

* the relative import of the Internet alongside other sources of information in shaping suicidal behaviour

Examples will be gathered of Internet use that has encouraged or facilitated suicidal behaviour and of that which has prevented this and facilitated coping or recovery. Computer access will be available at the interviews and where appropriate, participants will be asked to take the interviewer through sites accessed, identifying material that they viewed and their perceptions of this. Participants will also be shown selected prevention/ support sites and asked for their evaluations of these.

A topic guide will be used to ensure consistency and that the research aims are fully addressed, but minimal prompting will be used. Participants will be encouraged to raise issues they consider of importance, including any relevant additional areas not covered by the guide. In this way, data collection will be grounded in the viewpoints and experiences of interviewees without imposing meanings. Interviews will be conducted in small batches with analysis performed simultaneously. This will allow for an iterative process in which emerging questions and ideas will be incorporated into the topic guide and explored with subsequent respondents until a refined level of understanding is reached. Interviews will be conducted at the respondent's home or the University according to their preference.

Full ethical approval will be sought before undertaking the study and a protocol will be developed for use should a situation arise where a respondent became distressed or disclosed information indicating possible risk. This will be based upon protocols developed by the team for use in similar studies. The study team has clinical expertise (JP) and extensive experience of conducting research with vulnerable populations. These include studies exploring non-help-seeking in young adults with mental distress [14] and factors influencing choice of suicide method amongst individuals who have survived a near-fatal attempt [15]. In the latter study we assessed respondent well-being before and after the qualitative interview and found that most respondents found participation cathartic and reported an improvement in mood [18].

Interviews will be audio-recorded with participants' consent and transcribed in full. First, transcripts will be coded for emerging themes and analysis will proceed according to the method of constant comparison, data relating to each code being retrieved and compared within and across individuals. Analytical grids will be used to map out relationships between codes. Second longitudinal case studies will be prepared to explore how Internet use may evolve and impact upon suicidal behaviour over time. Case studies of negative and positive Internet use will also be prepared and contrasted to identify their key features.

References

[1] Durkee T, Hadlaczky G, Westerlund M CV. Internet pathways in suicidality: a review of the evidence. International Journal of Environmental Research and Public Health 2011. 8:3938-3952.

[2] Harris K, McLean J, Sheffield J. Examining Suicide-Risk Individuals who go online for

suicide related purposes. Archives of Suicide Research. 2009. 13:3, 264-276.

[3] Eichenberg C. Internet message boards for suicidal people: a typology of users. Cyberpsychology and Behaviour. 2008. 11:1, 107-113

[4] Hawton K, Rodham K, Evans E, Weatherall R. Deliberate self-harm in adolescents: self-report survey in schools in England. BMJ 2002. 325: 1207-11

[5] Hawton K, Williams K. Influences of the media on suicide. BMJ 2002. 325: 1374-5

[6] Luxton D, June J, Fairall J. Social media and suicide: a public health perspective. American Journal of Public Health 2012. 102:195-199.

[7] Bell V. Online information, extreme communities and internet therapy: Is the interne good for our mental health? Journal of Mental Health 2007.16:445-457.

[8] Florentine J, Crane C. Suicide prevention by limiting access to methods: A review of theory and practice. Social Science and Medicine 2010. 70:1626-1632

[9] Prior T. Suicide methods from the Internet. American Journal of Psychiatry 2004. 161(8): 1500-1501

[10] Alao A, Soderberg M, Pohl E, Alao A. Cybersuicide: review of the role of the Internet on suicide. 2006. Cyberpsychology and Behavior. 9(4):489-493

[11] Becker K, Mayer M, Nagenborg M, El-Faddagh M, Schmidt M. Parasuicide online: can suicide websites trigger suicidal behaviour in predisposed adolescents? Nordic Journal of Psychiatry 2004. 58:111-114.

[12] Biddle L, Donovan J, Hawton K, Kapur N, Gunnell D. Suicide and the Internet. BMJ. 2008. 336(7648): 800-802

[13] Recupero R, Harmss E, Nobel JM. Googling suicide: surfing for suicide information on the Internet. Journal of Clinical Psychiatry. 2008. 69(6): 878-888

[14] Biddle, LA, Donovan, J, Sharp, D & Gunnell, D. 'Explaining non-help-seeking amongst young adults with mental distress: a dynamic interpretive model of illness behaviour', Sociology of Health and Illness. 2007. 29 (7): 983-1002.

[15] Biddle, L, Donovan, JL, Owen-Smith A, Potokar, JP, Longston D, Hawton K, Kapur N & Gunnell, DJ. 'A qualitative study of factors influencing the decision to use hanging as a method of suicide', British Journal of Psychiatry. 2010. 197 (4): 320-325.

[16] Schwandt T. Three epistemological stances for qualitative inquiry: interpretivism, hermeneutics, and social constructionism. In: Handbook of qualitative research (ed N Denzin, Y Lincoln) Sage, 2000.

[17] Glaser B, Strauss A. The discovery of grounded theory: strategies for qualitative research. New York: Aldine De Gruyter, 1967.

[18] Biddle L, Cooper J, Owen-Smith A, Klineberg E, Bennewith O, Hawton K, Kapur N, Donovan J, Gunnell D. Qualitative interviewing with vulnerable populations: individuals' experiences of participating in suicide and self-harm based research. Submitted to Journal of Affective Disorders.

Building on the work of an existing, MRC-funded project examining the contributions of the ZNF804A zinc finger transcription factor locus to brain function in animal models, the work proposed here aims to apply recall studies to expand this effort to detailed examination of parallel human traits, combining the expertise and methods developed in MRC CAiTE with Cardiff's expertise in neuropsychiatric genetics and Bristol/Harvard's expertise in sleep neurophysiology. Crucial to the motivation of this study are the observations that (1) variation at the ZNF804A locus is associated with schizophrenia and related disorders risk and (2) that patients present with abnormalities in neural oscillations during sleep, which in turn cause or reflect cognitive deficits that respond poorly to current therapies. Since distinct patterns of oscillatory neural activity during sleep reflect functioning of well-defined neural circuits, this presents an opportunity to link ZNF804A variants to brain function and thereby rationalize future therapeutic design.

Objectives

1)To determine the impact of adolescent disordered eating behaviours on bone accrual and bone development throughout adolescence and young adulthood.

2) To determine the role of factors such as caloric restriction, delayed puberty, excessive exercise, gender in explaining the effect of disordered eating on bone health in adolescence.

3) To determine the impact of adolescent disordered eating behaviours on stress fractures in young adulthood.

Background

Eating disorders (ED) are chronic disorders and affect about 5-10% of the population (Hoek and Van Hoeken, 2003).

Adolescent ED and bone development: ED have a peak incidence in adolescence, a crucial time for physical and skeletal development. Pubertal years are the period in the life course when bone mass reaches its highest level. The level of bone mass attained at this age is a key determinant of long-term bone health and risk of osteoporotic fractures in later life (Ott, 1991).

Past research focusing on bone density in ED has shown that restrictive ED (such as anorexia nervosa (AN) and atypical anorexia nervosa/ Eating Disorder not otherwise specified-EDNOS) are associated with reduced bone mass. This is probably secondary to low weight, reduced fat mass and hormonal abnormalities secondary to poor nutrition (Misra, 2008; Mehler et al, 2011). Whilst recovery from the ED has been shown to lead to improvements in bone density, several studies show that bone density remains lower than in individuals who have not experienced an ED, particularly in cases where the ED onset was in adolescent years (Biller et al., 1989; Hartman et al., 2000; Wentz et al., 2007; Bolton et al., 2005).

Binge- type ED (such as bulimia nervosa and binge eating disorder) have been less well studied, and appear not to affect bone density to the same extent as restrictive ED, particularly if normal weight is maintained (Misra, 2008). However, higher fracture risk was also shown in these women compared to controls (Vestergaard et al., 2003).

Studies investigating bone density in adolescents with restrictive ED as measured by dual energy X-ray absorptiometry (DXA) have shown low bone density at the spine, hip and femoral neck (Misra, 2008); as well as reduced bone turnover. These effects are apparent in both girls and boys (Castro et al., 2002). Follow-up studies of adolescents have reported some improvement in bone density with nutritional restoration, mainly in areas of trabecular bone, such as the spine. Several studies, however, have shown fewer improvements in bone density at cortical sites despite recovery from the ED ((Herzog et al., 1993; Mika et. al, 2007). Given that the adolescent years provide a narrow window of opportunity in which to optimize bone mass accrual, disruption during these years might lead to permanent deficits.

Stress fractures:Although stress fractures are relatively uncommon, they affect as many as 15% of young women athletes and military recruits. Among females, other suspected risk factors for developing a stress fracture include disordered eating (Rosen et al, 1986) and irregular menstrual cycles, both which may result in a deficient estrogen status that can counteract the beneficial effects of exercise on bone density (Wolman et al., 1990; Lloyd et al. 2000; Bass et al.,1998).The combination of disordered eating, amenorrhea, and low bone density is characterized as the Female Athlete Triad. The recognition of the triad has served to increase awareness of bone health concerns among young female athletes (Yeager et al., 1993; Otis et al., 1997). Thus, it is extremely important to identify modifiable predictors of stress fracture so that prevention programs could be developed for high-risk populations.

Gaps in the literature:Most studies in the field to date rely on small clinical samples, and are likely to represent more severely ill subjects attending in- or out-patient services and not be generalisable to all ED. Length of follow-up has often been limited to 1-2 years. Moreover, DXA provides an overall estimate of bone mass but does not directly measure aspects like cortical thickness and cross sectional area that determine overall bone strength. Techniques like peripheral quantitative computed tomography (pQCT) can provide detailed information about cortical bone geometry and strength, but only one study to date has used this method to study bone changes in adolescents with ED (Milos et al.,2007). In light of recent finding that fat mass is an important positive determinant of cortical bone size and thickness (Sayers & Tobias, 2009), we are particularly interested in examining whether adolescent ED predicts weaker cortical bones due to reduced fat mass. More than half of adult bone calcium is acquired during adolescence and a woman's peak bone mineral density, a major determinant of her long-term risk of osteoporosis, is thought to be achieved by early adulthood. Therefore assessing bone density in young adulthood, as well as throughout adolescence, allows a better assessment of peak bone density. This additional investigation will allow a better understanding of the longitudinal effects of adolescent ED behaviours on bone development.

To our knowledge there are: no studies on a general population sample of adolescents/young adults able to link temporal relationships between disordered eating behaviours and bone development. Both would allow a clear identification of causal biological mechanisms, and take into account the role of confounders. The current lack of evidence impacts on available prevention and early treatment for patients with ED.

This study is unique in that data have already been collected prospectively and independently on bone density and ED behaviours in about 6,000 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC). This longitudinal prospective study will allow: (1) determining precise temporal relationships between predictor (ED behaviours) and outcomes (bone density, cortical bone size and thickness, peak bone mass, and stress fractures); (2) focusing on causal biological mechanism taking into account the role of confounders (thanks to the wealth of data available in ALSPAC).

Methodology

Theoretical/conceptual framework: This is a longitudinal study, which will rely on data prospectively collected as part of the ALSPAC study. The ALSPAC study is a longitudinal prospective cohort of 14,000 mothers and their children. Women were enrolled in the study in pregnancy. Children have been followed up at regular intervals from birth up to age 18.

Research questions:do adolescent disordered eating behaviours (not only clinical ED) negatively affect bone accrual and bone development during puberty and into young adulthood, including individuals with subclinical disorders not currently viewed as being at risk? Do reductions in fat mass contribute to these deleterious effects of ED behaviours on bone development particularly those on cortical bone? This being the case, are reductions in fat mass in the context of ED behaviours particularly harmful, reflecting the fact that they are achieved by dietary restriction as opposed to by increased physical activity? What is the impact of disordered eating behaviours on peak bone mass?

Methods:

Outcomes:

1) Total DXA scans have been performed on the children/adolescents at ages: 11.5 (n = 7159), age 13.5 (n = 6147), age 15.5 (n= 5509) and age 17.5 (approximately 4000). In addition, hip DXA scans have been performed at age 13.5 and 17.5, and pQCT scans of the mid tibia at 15.5 and 17.5. Standard DXA and pQCT parameters related to bone development have been derived and will serve as the main outcomes. Data on fractures has also been collected at regular intervals.

We are seeking funding for a new wave of data collection to collect:

1. a 1-page questionnaire on stress fractures;

2. a two page questionnaire (or computerised assessment) on disordered eating behaviours and participation in exercise

3. DXA (hip and total body) and pQCT (tibia plus radius)

4. objective measurement of weight and height

Predictors:

1) Data on adolescent ED behaviours have been collected at age 13, 14, 16, and 18 adolescents

Other explanatory variables (mediators and/or confounders):

1)- Data are also available on pubertal timing and anthropometric measures at all the above ages on ~6,000 adolescents.

-Total body fat and lean mass as measured by total body DXA

-Physical activity as measured in the children by accelerometry at multiple time points

-Detailed information on adolescent diet using a combination of diet diaries and food frequency questionnaires

-Extensive information on socio economic status

Data collection: we envisage the new data collection can be part of an ALSPAC clinic, alternatively we will select individuals on the basis of their exposure (any disordered eating in adolescence, N=600-800) and unexposed individuals (no disordered eating in adolescence, N=600-800) to assess.

Analyses: Univariate and multivariate logistic models will be used to determine the effect of relevant predictors on outcomes. Longitudinal modelling will be used for longitudinal repeated data and to model hypothesised relationships.

Aim: To carry out a genome-wide association study that takes into account not just lifetime asthma status but also the presence of hayfever.

Hypotheses: The power of asthma genome-wide association studies (GWAS) can be improved -- and so new susceptibility loci can be identified -- by defining cases and controls based on diagnostic criteria that are more refined than a simple doctor diagnosis of asthma. We hypothesise that the presence of hayfever in addition to asthma defines a subgroup of asthma patients that will help map new loci for allergic disease.

Independent variable: Individual genotyped or imputed SNPs located in the autosomes or X-chromosome, coded as allelic dosage.

Dependent variable: Binary phenotype (ie case-control status) with affected individuals defined as those individuals who reported in any of the available ALSPAC surveys (7.5 and 14 years) to have been diagnosed by a doctor with asthma *AND* reported in any of the available surveys (11 and 14 years) to have hayfever. So lifetime self-reported asthmatics with hayfever. Unaffected individuals are defined as those individuals who never reported in any survey to have asthma or hayfever.

Confounding variable: None.

Analysis plan: Perform association analysis of SNP dosage after applying standard QC filters (eg. MAFgreater than 1%, HW P-value greater than 10-6, call rate greater than 95%, imputation info/r2 greater than =0.3) and excluding samples of non-European ancestry. Analyse males and females separately and include SNPs on the autosomes and the X-chromosome.

Aims

1) To explore associations between early parenting and parental knowledge/monitoring of teenage behaviour.

2) To investigate associations between parenting and adolescent risk behaviour, with a view to establishing whether parental knowledge/monitoring mediates any associations between early parenting and adolescent risk involvement.

Background

Parental monitoring and knowledge of teenage behaviour have been widely identified as important protective elements limiting teenage risk involvement [1-8]. However, there is no consensus on processes covered by the terms parental knowledge or monitoring. Stattin and Kerr's work gave primacy to parental knowledge, emphasising the key role of children's disclosure of information [9-11]. Other work has indicated that parent-led behaviours, such as parental solicitation of information and rule-setting, may also be involved [12-14].

Comparatively little is known about what leads some parents to have lower levels of knowledge about their teenagers, or to monitor their children less attentively. A recent review of the relationship between parental monitoring and knowledge and conduct problems [15] has called for further research in this area. This review identified three main groups of possible antecedents to parental monitoring and knowledge: contextual, child characteristics and aspects of early parenting. Contextual factors influencing the level of monitoring/knowledge include the child's gender, family status, SES, ethnicity and neighbourhood; while child characteristics include early conduct problems, early antisocial behaviour and a difficult or "resistant to control" temperament. Both groups of factors have been relatively well studied. The focus of the current study is on the third group of antecedents, early parenting.

Various aspects of the parent-child relationship (parental trust in their child, authoritative parenting style, parental sensitivity/responsiveness) and time spent in family activities have been found to be associated with greater parental knowledge or teenage disclosure, but these have been studied only in teenagers [12, 13, 16-19]. Little is known about how parenting of young children may relate to parental monitoring and knowledge of teenagers. Two (related) studies have suggested the importance of early "proactive" parenting: averting potential problems in early childhood before they become entrenched [20, 21]. While anticipating behavioural problems seems to be a useful parental strategy that may lay foundations for successful monitoring of teenagers, the teenage research suggests additional qualities related to early parent-child connectedness and behaviour management may also be important.

Hypotheses:

1. Early parent-child connectedness and behaviour management will be associated with (respectively) greater teenage disclosure of information and greater parental control of a teenager's behaviour.

2. Teenage disclosure and parental control will both be associated with teenage risk involvement.

3. Early parenting will be associated with teenage risk, directly and/or indirectly via parental knowledge and monitoring.

Research using ALSPAC data set

Outcome measures

Stattin and Kerr measures of parental knowledge, parental solicitation, parental control and child disclosure were collected from the 13-year old clinic sample and from their parents. Child-reported teenage risk behaviour (antisocial behaviour, substance use and sexual behaviour) was collected from the age 15 clinic sample and questionnaires at a comparable age.

Main exposures

Measures of early parenting were collected from mothers at ages 2 1/2, 3 1/2 and 6 years, covering important aspects of parenting such as connection, conflict, autonomy, rule-setting, and discipline.

Potential confounders

Likely important confounders of associations between early parenting and parental monitoring and knowledge of teenagers include contextual factors (gender, SES, ethnic group, and family status), and childhood behavioural problems, risky friendships and involvement in antisocial behaviour. Maternal mental health, parental substance use, quality of partner relationship and child pubertal development will also be explored as potentially important confounders of associations between early parenting and adolescent risk outcomes.

References

1. Hoeve, M., et al., The Relationship Between Parenting and Delinquency: A Meta-analysis. Journal of Abnormal Child Psychology, 2009. 37(6): p. 749-775.

2. Dishion, T.J. and R.J. McMahon, Parental Monitoring and the Prevention of Child and Adolescent Problem Behavior: A Conceptual and Empirical Formulation. Clinical Child and Family Psychology Review, 1998. 1(1): p. 61-75.

3. Li, X.M., S. Feigelman, and B. Stanton, Perceived parental monitoring and health risk behaviors among urban low-income African-American children and adolescents. Journal of Adolescent Health, 2000. 27(1): p. 43-48.

4. DiClemente, R.J., et al., Parental monitoring: Association with adolescents' risk behaviors. Pediatrics, 2001. 107(6): p. 1363-1368.

5. Boyer, T.W., The development of risk-taking: A multi-perspective review. Developmental Review, 2006. 26(3): p. 291-345.

6. Li, X.M., B. Stanton, and S. Feigelman, Impact of perceived parental monitoring on adolescent risk behavior over 4 years. Journal of Adolescent Health, 2000. 27(1): p. 49-56.

7. Huebner, A.J. and L.W. Howell, Examining the relationship between adolescent sexual risk- taking and perceptions of monitoring, communication, and parenting styles. Journal of Adolescent Health, 2003. 33(2): p. 71-78.

8. Rai, A.A., et al., Relative influences of perceived parental monitoring and perceived peer involvement on adolescent risk behaviors: An analysis of six cross-sectional data sets. Journal of Adolescent Health, 2003. 33(2): p. 108-118.

9. Stattin, H. and M. Kerr, Parental monitoring: A reinterpretation. Child Development, 2000. 71(4): p. 1072-1085.

10. Kerr, M. and H. Stattin, What parents know, how they know it, and several forms of adolescent adjustment: Further support for a reinterpretation of monitoring. Developmental Psychology, 2000. 36(3): p. 366-380.

11. Kerr, M., H. Stattin, and W.J. Burk, A Reinterpretation of Parental Monitoring in Longitudinal Perspective. Journal of Research on Adolescence, 2010. 20(1): p. 39-64.

12. Fletcher, A.C., L. Steinberg, and M. Williams-Wheeler, Parental influences on adolescent problem behavior: Revisiting Stattin and Kerr. Child Development, 2004. 75(3): p. 781-796.

13. Soenens, B., et al., Parenting and adolescent problem behavior: An integrated model with adolescent self-disclosure and perceived parental knowledge as intervening variables. Developmental Psychology, 2006. 42(2): p. 305-318.

14. Wight, D., L. Williamson, and M. Henderson, Parental influences on young people's sexual behaviour: A longitudinal analysis. Journal of Adolescence, 2006. 29(4): p. 473-494.

15. Racz, S.J. and R.J. McMahon, The relationship between parental knowledge and monitoring and child and adolescent conduct problems: a 10-year update. Clin Child Fam Psychol Rev, 2011. 14(4): p. 377-98.

16. Smetana, J.G., et al., Disclosure and secrecy in adolescent-parent relationships. Child Development, 2006. 77(1): p. 201-217.

17. Keijsers, L., et al., Reciprocal Effects Between Parental Solicitation, Parental Control, Adolescent Disclosure, and Adolescent Delinquency. Journal of Research on Adolescence, 2010. 20(1): p. 88-113.

18. Willoughby, T. and C. Hamza, A Longitudinal Examination of the Bidirectional Associations Among Perceived Parenting Behaviors, Adolescent Disclosure and Problem Behavior Across the High School Years. Journal of Youth and Adolescence, 2011. 40(4): p. 463-478.

19. Darling, N., et al., Predictors of adolescents' disclosure to parents and perceived parental knowledge: Between- and within-person differences. Journal of Youth and Adolescence, 2006. 35(4): p. 667-678.

20. Pettit, G.S., et al., Predicting the developmental course of mother-reported monitoring across childhood and adolescence from early proactive parenting, child temperament, and parents' worries. Journal of Family Psychology, 2007. 21(2): p. 206-217.

21. Pettit, G.S., et al., Antecedents and Behavior-Problem Outcomes of Parental Monitoring and Psychological Control in Early Adolescence. Child Development, 2001. 72(2): p. 583-598.

The ALSPAC dataset can answer the research questions we have efficiently and quickly, and with many major scientific strengths. It is the largest sample of its kind which is longitudinal, has good measures of the relevant exposures (total volume of habitual physical activity and intensity of physical activity measured by accelerometry at age 11 and 13y), of confounders, and of outcome measures (cognitive measures, academic attainment, mental health and well-being as measured by the SMFQ and the SDQ). Almost all previous studies to address our research questions have suffered from a combination of small sample size, cross-sectional design, crude or biased measures of exposures and/or outcomes, limited consideration of confounders.Please note that we already have the data required, as part of an existing collaboration with ALSPAC on a Bupa Foundation funded secondary analysis (ALSPAC coapplicants Prof Ness, Dr Leary, Dr Joinson; data buddy Dr Northstone) of associations between physical activity and cognition, academic attainment, and mental health in typically developing 11-13y olds in ALSPAC. The current proposal adddresses essentially the same research questions, but in study participants excluded from our current study on the grounds that they have developmental disorders.

A longitudinal study starting in pregnancy is needed in order to determine if dietary patterns, or fatty acid deficiencies or excesses, increase risk of self harm and significant symptoms of anxiety in the perinatal period. Fatty acid compositional data from mothers and from umbilical cord has already been provided. Within this population, minor alleles of the FADS 1-2 gene complex have been shown to associate with functional deficits in fatty acid metabolism corresponding to the delta 5 and delta 6 desaturases. Dietary patterns covary with essential fatty acid status and may be critical determinants. These fatty acids act as precursors for endogenous cannabinoids, which are implicated in depression anxiety and suicideal behaviors. Gene variants in the endocannabinoid pathway will be evaluated for association with self harm phenotypes. Data characterizing self harm phenotypes are available for development. No other study has this complement of datasets in a large well characterized representative population. This work is a continuation of analysis of existing data in project B275.