Proposal summaries
B1323 - Heavy metal levels in mothers during pregnancy and their effect on offspring cognitive ability - 15/03/2012
Previous studies have suggested adverse effects of arsenic and lead exposure (even at low levels) on children's cognitive function, including lower IQ scores, impaired attention and memory, and behavioural problems (Lanphear et al., 2005; Rosado et al., 2007). Copper deficiency during gestation can negatively affect motor function, balance and coordination (Georgieff, 2007), whilst excessive free copper may play a role on adult cognitive decline (Salustri et al., 2010). Methylmercury is a known neurotoxicant that can be found as a contaminant in fish. However, it has been difficult to assess its effects on cognitive ability independently of the beneficial effects of fish intake (Daniels et al., 2004).
Aims: To examine the role of prenatal and postnatal levels of metals on the cognitive development of children. We will use genetic variants robustly associated with serum concentrations of arsenic, copper, lead and mercury, identified through genomewide association studies (GWAS), as proxies for these exposures and investigate their association with offspring IQ scores and school test results.Hypotheses: We hypothesise that alleles which increase levels of circulating toxic metals such as arsenic, lead and mercury will be associated with a worse performance in cognitive tests. With respect to copper, both high and low serum levels could potentially lead to an adverse cognitive outcome.
B1322 - Births out of wedlock and cognitive and social development throughout childhood a quantative analysis - 15/03/2012
Research design: We have already coded a wide range of behaviours in the video material obtained from the 60 families of children who developed psychiatric disorders, together with 120 control videos. The full dataset was sent to the ALSPAC team, who have added the data to their own database.
1. Clinical rating scale. We first plan to investigate the cases of inattentive ADHD and pervasive development disorder (PDD) / autism in much more depth. We have been provided with the identifiers for these cases and have been given permission for expert clinicians to perform detailed assessments of the videos. This should allow us to build up a diagnostic system for testing and for potential use by clinicians after testing in a longitudinal design. Analysis of sequencing and contingency in these videos will allow us to explore whether there are differences in the behavioural dynamics of mutual responsiveness in early face-to-face mother-infant interactions in infants who later go on to be diagnosed with ADHD or PDD. We shall first ask a group of clinicians (CG, CP, PW and Dr Helen Minnis) and a developmental psychologist (HM) to view the videos of the inattentive ADHD and PDD cases (and 33 sex-matched control videos) and identify behaviours that appear predictive of disorder in order to develop a diagnostic rating scale. A second group (5 General Practitioners & 5 Health Visitors) will view the 11 case videos and 33 control videos and be blind to the case and control status of the videos. They will use their own judgments to predict which infants will later go on to develop inattentive ADHD or PDD. Then this second group will look at the videos again, this time using the rating scale developed by the group 1 clinicians. The second group of clinicians will take part in this study as part of a CPD knowledge transfer protocol (a 2 day course). The findings from this study will have a direct potential impact for routine practice.
2. Adult motor activity. In view of the finding, using our holistic ratings, that adult hypoactivity predicts childhood disruptive behaviour disorders (ADHD and oppositional/conduct disorders), we wish to collect objective evidence on adult movement in the 180 videos in the same way that we have done for infant motor activity, using frame-by-frame analysis aided by SkillSpector software. Frame-by-frame locations (x-y coordinates, in pixels) of the adult's hands, elbows, shoulders and nose will be taken from all of the 180 videos. Methods of processing this information have been developed, including measures of total motion, average velocity and acceleration. We need to assess all 180 videos to give us robust comparisons and linkable data for adult and child. The relationship between motor activity, maternal depression and parenting behaviours will be investigated.
3. Sequencing. Once we have collected data on motor activity in the adults we shall investigate the sequencing of both infant and adult motor behaviours and of the infant and adult vocalisation behaviours we have already obtained with a view to establishing if there are particular patterns of disruption of social interaction which can be characterised objectively and which are associated with psychopathology. There is a strong a priori case that abnormalities will be found in cases of autism as well as some cases of ADHD.
Sex-adjusted logistic regression models will be used to estimate the odds ratios for the subsequent development of disorders associated with maternal and infant movement and their inter-relationship. Multivariate regression models will be used to determine the degree of confounding between measures and develop a subset of measures with independent predictive value for each group of cases. The predictive ability of the resultant scores will be summarised in terms of standard measures of diagnostic utility, including receiver operator characteristic curves.
B1319 - Depression obesity dietary patterns and gestational weight gain during pregnancy - 15/03/2012
Aims: We will examine the relationships between antenatal mental health, BMI, diet quality and GWG. We aim to investigate whether pre-pregnancy BMI and mental health problems during pregnancy are related to poor quality diet (both dietary patterns and nutritional intakes) and excessive GWG.
Hypotheses: We hypothesise that, after adjusting for potential confounders: 1) A less healthy dietary pattern (higher proportions of energy dense foods and lower proportions of vitamin rich foods) and more excessive GWG will be reported by women with antenatal depression and anxiety compared with women without mental health problems. 2) A less healthy dietary pattern (higher proportions of energy dense foods and lower proportions of vitamin rich foods) and more excessive GWG will be found in overweight/obese women compared with normal weight women. 3) A less healthy dietary pattern (higher proportions of energy dense foods and lower proportions of vitamin rich foods) and more excessive GWG will be reported by high BMI women with depression/anxiety compared with high BMI women without these mental health problems. The interaction between BMI and mental health will be investigated.
Analysis:The effect of mental health on diet quality and GWG will be examined in the sample as a whole and in subgroups of women with normal (18.5-25kg/m2) and high (greater than 25kg/m2) pre-pregnancy BMI. The interaction between mental health and BMI will be investigated. The effects of socioeconomic status, maternal age, smoking and other confounders will be examined.
B1318 - Longitudinal determinants of bone growth and coassociations with body composition - 01/03/2012
Aims: Using a combination of simulation and empirical examples we hope to explore the consequences of many of the assumptions used in the previously mentioned methods. We specifically will investigate the suitability of displacement models (vertical growth, and bone mass accrual) to characterise first derivates, i.e. peak height velocity and peak bone velocity, and second derivatives i.e. growth acceleration, and contrast the conclusions made under different methods. In addition, we intend to investigate the simultaneous relationship between changes in body composition and bone growth using cross-lagged methods.
We aim to emphasize the importance of using appropriate methods in order to make robust conclusions.
The primary exposure in all analyses are time, outcomes include height, long bone length, bone mass, fat and lean mass. Similarly confounding variables are the same as the potential outcomes, as changes can occur simultaneously.
B1316 - Intimate Partner Violence and Abuse IPVA in Adolescent and Young Adult Relationships Phase One - 16/02/2012
Our proposed ALSPAC study consists of two analytical phases.
Phase One will measure the prevalence of IPVA and identify the characteristics of intimate partner violence and abuse for different age groups (age 13, 13-18, 18-21) and in relation to sociodemographic and socioeconomic factors in the ALSPAC cohort. We aim to examine the overlap between experience/perpetration of potential IPVA behaviours for under-18s and over-18s. In addition, we shall examine the possible associations between physical violence experienced or perpetrated at age 13 (existing questions) and IPVA behaviours experienced and perpetrated under the age of 18 and between 18-21 (new questions).
The aim of Phase Two is to contribute to a more comprehensive understanding of the mechanisms underlying the transmission of risks and protective factors associated with the exposure to domestic abuse in childhood and IPVA in later life. A longitudinal study with a nested qualitative study will inform a more nuanced understanding of the complexity of the effects of direct and indirect experiences of IPVA, and their possible associations with adolescent and young adult outcomes. This Phase is not developed further in the current proposal.
B1315 - Does maternal sensitivity in infancy actual or feared separation in childhood affect adolescent antisocial behaviour - 16/02/2012
Aims: This research aims to explore the longitudinal relationship of maternal sensitivity in infancy on the development of adolescent ASB. It explores whether this relationship is mediated by separation from caregiver and/or feared separation (separation anxiety).
Research Question: In more specific terms it aims to answer the following question: does maternal sensitivity in infnacy and actual or feared separation in childhood affect adolescent ASB?
Hypotheses: The research will test four hypotheses: 1. A) Poor maternal sensitivity between mother and infant will increase the number of ASB incidents engaged in by the child in adolescence. It is predicted that positive maternal sensitivity observed in childhood will decrease the number of incidents of ASB in adolescence. B) Negative maternal sensitivity will be associated with a greater number of ASB's across all four domains: aggression, destruction of property, deceitfulness and theft, and serious rule violation (Barker & Maughan, 2009), with a greater number of acts towards others. 2.The number of periods of separation of the child from the caregiver increases so will the likelihood/risk of later adolescent ASB. 3. There will be a greater number of incidents of adolescent ASB recorded for children who exhibit separation anxiety than children who exhibit no separation anxiety. 4. The type of adolescent ASB and the number of adolescent ASB incidents will be mediated by gender.
B1314 - Alcohol and substance use risk development and desistance during transitions to adulthood - 16/02/2012
Structure. The research programme will be organised around four work-streams. In addressing transitions to adulthood, contextual effects and variation are important, so our first work-stream centres on these. The second addresses the balancing issue of individual genetic effects. Since experience of tertiary education is pivotal for many, has increased markedly for the relevant cohorts, and is under-researched, the third stream looks specifically at this. Cross-national contextualisation is important, both to inform policy intervention and understanding of processes, so work-stream four deploys the team's expertise to provide this context. All four work-streams connect to issues of methodological development, and of implementation of prevention, and two final, cross-cutting themes, consolidate these issues.
1. Trajectories and outcomes of alcohol and substance use in the transition to adulthood.
2. The impact of genetic risk across different social contexts.
3. Substance use and the transition to third level education.
4. Regional and international comparisons of alcohol and substance use behaviours and risk pathways during the transition to adulthood.
Cross cutting theme 1: methodological development.
Cross-cutting theme 2: Effective prevention.
B1313 - Lifecourse trajectory of muscle strength and the relationship with physical activity - 16/02/2012
The aims of the proposed Research Fellowship are as follows: 1. To describe a lifecourse grip strength trajectory from childhood to old age, by combining data from several UK cohorts 2. To compare the influence of physical activity on grip strength at different ages across the lifecourse 3. To explore the relationship between physical activity and subsequent grip strength trajectory. Evidence, mainly from age-heterogenous cross-sectional studies1 suggest that muscle strength, as assessed by grip strength, increases through childhood and adolescence, reaching a peak in early adult life before declining with increasing age. As no one cohort has repeated measures of strength for the same individuals from childhood to old age, it is necessary to combine repeated measures from several cohorts in order to construct a lifecourse trajectory of muscle strength. The cross-council funded HALCyon cohort consortium has already harmonised measures of physical capability, including grip strength, in eight UK cohorts spanning ages 50-90+ years.2 Similarly, the FALCon project has worked to develop and disseminate methods for the lifecourse modelling of physical and cognitive function, as well as cardiovascular function such as blood pressure.3 There is therefore the opportunity to continue work from both projects to look at the lifecourse trajectory of grip strength. In childhood and adolescence, we hypothesise that higher levels of CPA may predict a higher absolute values of muscle strength as well as a greater relative increase in strength towards the subsequent peak in early adult life. We also hypothesis that higher levels of CPA will be prospectively associated with slower declines in muscle strength in adulthood.
B1312 - Birth order and cardiovascular risk factors a comparison between the Pelotas cohorts and ALSPAC - 16/02/2012
Birth order and cardiovascular risk factors: a comparison between the Pelotas cohorts and the Avon Longitudinal Study of Parents and Children
Main research questions
1. Is there an association between birth order and CVD risk factors in ALSPAC? 2. Is the association between birth order and CVD risk factors consistent across the 3 Pelotas cohorts 3. What differences in the confounding structure could explain the different associations in ALSPAC and Pelotas (and potentially across the three Pelotas cohorts)
Analysis plan 1.Is there an association between birth order and CVD risk factors in ALSPAC?
2.Is the association between birth order and CVD risk factors consistent across the 3 Pelotas cohorts ?
3.What differences in the confounding structure could explain the different associations in ALSPAC and Pelotas (and potentially across the three Pelotas cohorts)
B1310 - Relationships between childhood social environment and sexual maturation and the role therein of the IGF axis - 02/02/2012
Objectives
- Derive a measure of social adversity prior to five years of age (see Nettle et al. 2011)
- Determine whether social adversity predicts age at sexual maturity/peak height velocity
- Determine whether social adversity predicts attitude to sexual relationships in adolescence and risk-taking behaviour
- Determine whether social adversity predict the age at/probability of the cohort member first having sexual relationships
- Determine whether social adversity predicts IGF-I and IGFBP-3 measured at age 5/8
- Determine whether IGF-I and IGFBP-3 measured at age 5/8 mediate or moderate the relationships described in 2-4 above
B1309 - Essential fatty acid status alcohol and tobacco misuse and genetic variance in candidate pathways - 02/02/2012
Objective 1. To determine if essential fatty acid levels during pregnancy, or at age 7, are associated with alcohol and tobacco misuse in late adolescence.
Objective 2. To determine if essential fatty acid levels during pregnancy, or at age 7, are associated with candidate intermediate behavioural phenotypes that increase risk for alcohol and tobacco misuse in late adolescence.
Objective 3. To determine if genetic variations in candidate pathways are associated with increased risk of intermediate behavioural phenotypes and increased risk for alcohol and tobacco misuse in late adolescence.
B1307 - Exploring the relationship between perinatal depression disorganised feelings of attachment and child outcomes - 02/02/2012
Aims/Objectives: The study aims to investigate; The independent associations between antenatal and postnatal depression and maternal feelings of disordered attachment; Whether the disordered attachment feelings of mother-infant interactions are associated with child outcomes.
Importance: Depression is experienced by 10-15% of women during pregnancy and after birth. Both antenatal and postnatal depression has been associated with multiple negative mental health consequences for the child. Evidence suggests that postnatal maternal depression leads to these poorer outcomes, in part, through disruption to maternal behaviour and disordered mother-child relationships. Our recent investigations in ALSPAC also suggest that antenatal depression may disrupt preparations for motherhood and as such the mother-infant relationship after birth. It is therefore important to gain further insight as to how both antenatal and postnatal depression disrupts the mother-infant relationship. It is also important to understand which aspects of the mother-infant relationship are important to child development. Implications: Although, we would expect to find many mothers, who answered yes to the attachment feelings question, to have a high depressive symptom score, by coding the free text according to further categories, it will be possible to see if antenatal and postnatal depression relate to different aspects of disordered attachment feelings. In addition understanding which categories of disordered attachment feelings in the mother-infant relationship are important to the future development of the child
B1306 - Genetic distance and intelligence - 02/02/2012
I have developed a mathematical technique which reveals "global" information about the distribution of causal variants for aquantitative trait. It is similar to the Visscher technique for extracting heritability, in that it does not identify specific loci, but rather properties of their distribution. I have done some preliminary work with this technique on height data, and it seems tobe giving very nice results -- we have indications about the density of alleles as a function of MAF, their average effect size and the total number.
I do not need full access to the SNP level data to do the analysis. At minimum I need a small amount of time from someone who is familiar with computations on such data. I can explain what I need to have computed in a relative brief conversation, and it can run on an ordinary PC or even laptop. Once the resulting set of numbers is reported back to me I can produce the results which characterize gene-level distributions. No information regarding individual genotypes need pass to me.
B1305 - Risk factors for substance use in early adolescence Is there a protective role of organised activities - 02/02/2012
Aims: To identify factors that are major predictors of adolescent substance use and develope propensity scores based on these risk factors. Additionally it is of interest if involvement in organised activities is related to propensity scores and adolescent substance use. Another aim is to establish if psychological theory can explain this relationship by examining whether measures of cognitive development vary by those who have a high or low score of risk.
Hypotheses: 1. Organised activities have differential effects on risky behaviour by vulnerability to risk. 2. Psychological factors underpin the relationship between organised activities and their effects on risky behaviour.
B1304 - Association of early life infection with childhood growth measures and cognitive abilities - 02/02/2012
Aims: A critical period for important processes involved in brain development, such as synapse and dendrite formation, neural pruning, and myelination, begins in utero and continues through the first few years of life. Infection in infancy may compete with bodily resources that are otherwise necessary to promote normal growth and development during this critical period. We aim to evaluate whether a mother's report of her baby's infection during the first 6 months of life is associated with birth weight and early childhood growth patterns, whether infection is associated with cognitive measures in childhood, and whether the association of infection with cognitive measures can be explained in part by slower growth patterns.
Hypotheses:1. Increased infection in infancy will associate with lower birth weight and slower childhood growth trajectories. 2. Increased infection in infancy will associate with poorer performance on cognitive tests. 3. The association of increased report of infection with lowered cognitive test performance will attenuate after control for growth measures.
Exposures: Maternal report of baby's infection during the first 6 months. We wish to use latent classes of infection as defined by Hepworth et al. 2010 EJE. Outcomes: Clinic and parental report of height and weight measures from birth to 10 years; WPPSI at 4 years and WISC-III at 8 years of age; Strength and Difficulties Questionnaire; other tests of memory, attention and developments (see data required above) ; we will consider educational outcomes as they become available.
B1301 - EXPOsOMICS - 30/01/2012
(No proposal received).
B1299 - TwinsUK - management of samples - 25/01/2012
TwinsUK is an international genomic epidemiology resource started in 1992. This Adult Twin Registry contains 11,000 volunteer population-representative twins with basic phenotypic information. 7,000 twins have both extensive phenotypic and genomic data, including 3000 individuals with next generation sequencing. This aims of this application are to:-
1) Maintain TwinsUK, including the core staff, twin register, and twin engagement, to facilitate use of the resource in ongoing and new projects.
2) Open and enhance the TwinsUK resource for the wider scientific community by inviting applications for new phenotypes and collecting and storing fibroblasts during a new data colletion sweep in 2013-2015.
3) Continue and improve ongoing access to data and samples from more than 20 years of TwinsUK collection. Extend the current model of supported access towards a full open accss model for TwinsUK data. This will expand on current work on the WT/MRC UK10K project (50 phenotypes with open access) to enable external academics maximal access to data already collected.
4) Further develop the resource by upgrading the extensive biobank of biological samples stored by TwinsUK into a robotic facility to ease sample availability under supported access, and ensure secure sample backup and replacement for sustainable long-term use.
B1298 - CFS National Outcomes Database and Biobank - 12/01/2012
This resource will exploit the CFS/ME National Outcomes Database (NOD), which collects data at clinical assessment (2,000 cases per year) and follow-up from NHS specialist CFS/ME services in England. The NOD will have phenotypic data on ~7,000 patients with link with CFS/ME at the start of the study (October 2012). BioME will add data ~7,500 patients and link with phenotypic data collected from two large randomised controlled trials (1,2) creating a database with data on ~15,500 patients. We will contact all patients who have contributed data (2006-2012), and all new patients (2012-2017) attending 19 specialist CFS/ME services, to collect saliva samples (by post) and extract genomic DNA (~9,400 samples). Research nurses in 4/19 services will also collect blood into clotted, EDTA and PAXgene tubes (fractions: serum, plasma, buffy coat, red cells, RNA) and urine from 1,000 patients. This large collection of phenotypic data and biological samples will enable researchers to perform: genome wide assocation studies (GWAS) and epigenetic, metabolomic and proteomics studies using samples from CFS/ME patients with well-characterised phenotypes and long-term outcome data.
B1297 - Prevalence of Chlamydia infection at age 17/18 and its association with socioeconomic position and other characteristics - 12/01/2012
In particular the proposed study will investigate the following gaps in available evidence:
- Limitations in the evidence base on prevalence of Chlamydia infection.
- Is there a relationship between socioeconomic position and Chlamydia positivity and does this vary according to whether income, social class or maternal education measures are used?
Overall aim: 1. To describe the prevalence of Chlamydia infection and to investigate its association with socioeconomic position and other characteristics.Specific objectives: 1.To describe the sex-specific prevalence of Chlamydia at 17/18 years and its patterning by socio-demographic characteristics. 2. To investigate whether Chlamydia positivity varies by different aspects of socioeconomic position.Outcome: Chlamydia positivity at 17/18, identified through nucleic acid amplification test NAAT
B1292 - Effect modification of asthma and allergies by GST genotypes in children living in a mouldy environment - 10/01/2012
We are aiming to investigate whether GSTP1 polymorphism modifies risk for asthma and allergic health outcomes including allergic rhinitis and allergic sensitization associated with visible mould in six birth cohorts. Recent publications support the hypothesis that genetic variants in genes related to the cell protection controlling the inflammatory and antioxidative systems may modify the risk for allergic respiratory diseases including asthma and rhinitis. Oxidative stress is believed to impair pulmonary function and Gluthathione S-transferase (GSTs) genes might be critical in the protection of cells from oxidative stress. ...). There might be a joint effect of domestic mould exposure and genetic variants in the pathogenesis of allergic diseases, similar as observed for exposure to ambient air pollution.
Exposure: visible mould between birth and 2 years of life at home
Outcomes: Asthma Symptom Complex (Physician-diagnosed asthma, wheezing, asthma medication): early (0-2y), school-age (6y), ever (3-10y). Wheezing: early (0-2y), ever (2-10y).Dry cough: (0-2y), ever (2-10y). Symptoms of Allergic Rhinitis: early (0-2y), school-age (6y), ever (3-10y). Allergic sensitization aero-allergens: school-age (6y).
After harmonizing exposure and health outcomes information, meta-analyses with fixed and random effect models will be applied.