Proposal summaries
B1229 - Using Mendelian Randomisation to Establish the Causal Role of Cigarette Smoking in Anxiety and Depression - 11/08/2011
Aim :To establish whether cigarette smoking causally influences risk of depression, self-harm and suicide
We will use rs1051730 / rs16966968 as a genetic instrumental variable to establish whether cigarette smoking causes depression, self-harm and suicide.
We hypothesise that the risk allele for heavy smoking will be associated with increased depression and it's sequelae, that this association will be fully accounted for by cigarette smoking, and that this association will not be observed in non-smokers.
Aims: To investigate whether the contribution of cigarette smoking to depression varies with age.
Based on evidence from preclinical studies relating to the sensitivity of the adolescent brain to nicotine, we hypothesise that cigarette smoking increases the risk of depression, and that this risk is greater in adolescence than adulthood.
To investigate the use of linkage of administrative data to corroborate outcome status.
Where available, we will use linked administrative data (e.g., electronic patient records, Hospital Episodes Statistics database) to corroborate outcome / exposure status, and explore whether classifications based on these influence apparent effects of exposure.
B1228 - Genetics prices and addiction - 11/08/2011
An economics literature has examined several determinants of addiction to cigarettes, including family habits, prices and discount rates. One area which is currently underexplored within this setting is the role of genetics in addiction formation. Both prices (Gruber & Zinman, 2001) and genes (Ding et al, 2009; Fletcher & Lehrer, 2011) have been found to drive smoking behaviour, but the interaction has not been explored. Our project will investigate how individuals differ in their response to health policies based on prices, and how genetics play a role in this.
In stage one of the project, we hypothesise that two mechanisms interact to partially determine the habit formation of smoking and other drug taking for young ALSPAC members. Firstly, young individuals consider the price of cigarettes when deciding whether to smoke. We will exploit price changes along two dimensions. As cohort members age, changes in taxes on cigarettes vary the price. Additionally, the ALSPAC children were born across a 21 month period and consequently for a given age, the price of a cigarette will vary. This will allow us to identify the effect of price changes upon the first age of smoking.
Secondly, an individual's response to their first cigarette will depend among other things, upon their genotype. Variations in both the speed of nicotine metabolism and dopamine and serotonin transmitters create heterogeneous adverse or positive reactions of a first cigarette, and subsequent dependence. We will investigate whether the response to a price change is less effective in individuals with certain genotypes.
In the second phase of the project we will explore the implications for the ALSPAC children of forming an addiction. Nicotine, alcohol or cannabis can themselves have detrimental effects on individuals. Retrospective information on smoking habits, prices and genotype will be combined with outcomes for 16 year old children. We will explore the effect on behavioural outcomes, obesity, expectations for the future, achievement against test scores and criminal activity. The methodology will exploit genetic variations in an instrumental variable setting. Assuming that genotype drives child outcomes only through its effect on smoking dependence allows estimation of the causal effect of addiction.
There are important policy implications inherent in this study. If the responsiveness of drug dependence to price changes varies across genotype, a group of individuals will require stronger intervention methods than prices alone. This is particularly true if we find adverse effects of forming an addiction on later outcomes for children.
Variables
We plan to make use of the genetic information for mothers and children of ALSPAC. The gene CYP2A6 drives the metabolism of nicotine and cotinine as well as other drugs and toxins.[1] There are different variants of activity of CYP2A6, and ALSPAC contains data on two in particular - CYP2A6*2 and CYP2A6*9 - which indicate slow functionality. CYP2A6*2 and CYP2A6*9 was measured for children and mothers. Lerman & Berrettial (2003) note the importance to control for maternal genes in order to separate the effects from the child's inherited genotype and familial smoking behaviour which is driven by parental genes. We would therefore request the genotype data for both generations. We hypothesise that children with differing activity of the gene will have different responses to smoking the first cigarette, and subsequent development of a smoking habit. Smoking is indeed found less likely in individuals with these variants and, for those who do smoke, quantities reported are lower[2]. Also, through its metabolism of other toxins, variants of CYP2A6 may drive the response to other drugs including alcohol and cannabis.
In addition, two genes contained in the ALSPAC genotyping archive which link to dopamine and serotonin transmitters are
SLC6A4 (5HTT) and MAOA. Variants in these genes lead to differential signals of pleasure upon consuming drugs, which again may drive the early stage addiction and dependence to the drugs.
At ages 14 and 16 questionnaires recorded the age ALSPAC children first smoked, drank an alcoholic drink and took drugs, the intensity with which they consumed them and records how the drugs affected them. For example, there is information on whether they felt ill after smoking. We will explore whether the reaction to the first experience of a drug differs by genotype.
The confounding variables are grouped into several categories. We will control for family smoking habits through the history of maternal and partner's reported smoking status. This will be important to the extent that children mimic the smoking behaviour of their parents. Additionally, as smoking behaviour is non-random across socio-economic groups we will control for education and occupation of parents. It is a concern that smoking behaviour is indicative of discount rates, whereby individuals with high discount rates place little weight on future periods relative to the present. To control for this, we will utilise the variables on diet, fitness and gambling.
[1]Hughes et al (1984), Ingelman-Sundberg, Nakajima M, Yamamoto T, Nunoya K, et al.(1996), Messina ES et al (1997), Benowitz NL, Jacob P III (1994).
[2] Schoedel et al (2004).
B1227 - Plasma protein and fatty acid biomarker discovery and validation programme for psychosis and the prodrome of psychosis - 11/08/2011
Aims:
1. We aim to identify plasma protein and fatty acid biomarkers of conversion to the prodrome or psychosis at age 17.
2. We aim to test the validity of these biomarkers as predictors of future conversion in the age 12 samples of the same subjects.
B1224 - The sources of vitamin A D and energy in the diets of pre-school children - 04/08/2011
Aim: To assess the sources of vitamin A and D in the diets of 18 & 43 month old children in comparison to energy intake in core & non-core foods. To provide evidence for dietary recommendations with regard to Vitamin A & D intakes.
Hypothesis: Core foods will supply more of the nutrients than non-core foods but less of the energy.
Dietary Vitamin D levels will be related to Vitamin D status as measured in blood samples collected at 43 months (This will only be done if blood levels of Vitamin D are already available or we can raise separate funds).
The quality of the diet with respect to Vitamins A and D will be related to socioeconomic postion and family make up.
Variables required: Dietary diary data for the children in focus subsample at age 18 & 43 months. Antropometric measurement for these children at both ages and blood levels of Vitamin D if available.
B1222 - The effect of snoring mouth breathing apnoea adenoidectomy and tonsillectomy on face shape PhD - 04/08/2011
Aims: To explore the effect of sleep disordered breathing in early childhood on face shape at age 15 years and to evaluate the effect of adenoidectomy and tonsillectomy on face shape.
Hypothesis: Sleep disordered breathing in early childhood, tonsillectomy and adenoidectomy have no effect on face shape in late adolescence.
Background: Sleep disorder breathing manifesting as mouth breathing, snoring and sleep apnoea has been of interest to orthodontists for decades as restricted nasal breathing tends to result in significant facial changes particularly increased face height with retrusive chin. However, removal of adenoids and tonsils has been reported as having a significant effect on obstructive breathing and if conducted early will normalise dentofacial morphology. Most of the previous studies have involved small samples (less than 20) and the facial parameters determined by lateral skull radiographs. The ALSPAC resource provides the opportunity to explore a longitudinal data set with detailed facial morphometry measures in late childhood on a large, representative sample of children.
We will explore the effect of sleep disordered breathing at ages 0-6 years on three-dimensional face shape at 15 years of age.
The principal outcome measures will be changes in upper and lower face heights as well as prominence of the nose maxilla and mandible. Differences in the 22 facial landmarks (x, y and z) between the various groups will be evaluated as well as comparison of mean three-dimensional facial shells for each subgroup. This should provide a comprehensive evaluation of the effects of sleep disorder breathing and removal of adenoids and tonsils on face shape.
B1221 - The role of environmentally induced epigenetic variation in childhood ALL susceptibility - 04/08/2011
The objective of this project will be to determine the ability of early life exposures to induce leukaemia-associated DNA methylation changes in apparently normal cells, which may increase the individual's likelihood of subsequently developing childhood leukaemia. Identification of such links might provide a plausible biological mechanism by which early life exposures could increase leukaemia risk and provide a rational basis for future dietary/environmental interventions aimed at reducing the development of abnormal DNA methylation and thus reducing the risk of leukaemia.
Specific aims: (i)Measure DNA methylation in a panel of genes (that we have previously identified as showing variation in childhood leukaemia cases) in cord blood DNA from a large, intensively characterised birth cohort and relate these findings to a wide range of exposures reported to influence leukaemia risk. (ii)Conduct allele-specific analysis of variation in DNA methylation to determine the allelic distribution of DNA methylation and whether this includes the appearance of highly methylated alleles, similar to those observed in full blown leukaemia.
B1202 - Association of the mu-opioid receptor and DRD2 genes with body weight in parents and children - 02/08/2011
In the literature there currently exist two diametrically opposite hypotheses; while one school of thought argues that obesity is associated with hyper-responsivity or excessive 'wanting' for food, another line of argument postulates that obese individuals are in fact hypo-sensitive to the rewarding properties of food. This latter hypothesis is informed by evidence that the dopaminergic system is downregulated in the obese, which, in turn, is believed to lead to chronic over-consumption of food as a means to compensate for the deficit. Aims and hypotheses: With respect to the above proposed studies investigating the opioid and dopaminergic systems, in the first instance it will be of critical importance to demonstrate that the candidate genes (OPRM1 and DRD2) are associated with obesity. The proposed pilot work will enable us to determine whether associations exist between OPRM1, DRD2, and obesity and we feel that these data will add a major strength to our subsequent grant proposal. On the other hand, if we were to find support for the null hypothesis, that these genes are not associated with obesity, then we would not pursue this line of enquiry. Either way, we feel that the scientific quality of our proposal will be greatly enhanced through the procurement of this pilot data from the ALSPAC cohort. We aim to examine data from ALSPAC on genotype (OPRM1, DRD2) and body fatness in the children and mothers. Specifically, we are interested in data on BMI waist circumference and body fatness at all available time points within the ALSPAC cohort. Our analyses will determine the extent to which OPRM1 and DRD2 genotypes are associated with these variables, both cross-sectionally and longitudinally.
B1199 - The genetics of cerebral asymmetry and handedness - 02/08/2011
Based on the results of our GWAS, we are interested in further dissecting the relationship between handedness and neurodevelopmental disorders such as dyslexia. We found an association between relative hand skill and PCSK6, specifically in individuals with dyslexia. Inclusion of individuals from ALSPAC with SLI and ADHD resulted in a stronger association. We are proposing to analyse the ALSPAC GWAS data for the pegboard measure specifically in those individuals we previously identified as having dyslexia, specific language impairment (SLI), or attention deficit hyperactivity disorder (ADHD).
We would first analyse those individuals defined as having dyslexia (N=238) genome-wide, then perform a meta-analysis with our own GWAS data. Following this, we can then replicate individual SNPs in our sample of unrelated dyslexic cases characterised with the pegboard measure (N=385). We will then extend the analysis to the larger group classified for neurodevelopmental disorders including SLI, ADHD and comorbid cases.
Our hypothesis is that the genetic basis of handedness, cerebral asymmetry and neurodevelopment are interlinked. SNPs associated with handedness in individuals with a neurodevelopmental disorder such as dyslexia may therefore be different to associated SNPs in a general population cohort.
B1217 - Self-harm with and without suicidal intent in school-aged children causes and consequences a 3 year follow-up of the ALSPAC cohort - 29/07/2011
We propose undertaking new data collection and analysing existing data to address the following research questions relating to self-harm in ALSPAC: 1.) What are the health and educational outcomes in children reporting self-harm with and without suicidal intent at ages 11 and 16. 2.)What is the influence of a) help-seeking, b) exposure to self-harm in friends and family, c) autobiographical memory, d) personality traits such as impulsiveness e) media/Internet exposure and f) non-suicidal self injury in mediating progression from suicidal thoughts and non-suicidal self-harm to suicide attempts from age 11 to 16 and from age 16 to 18. 3.) What are the differences and similarities between people who attempt suicide and those who carry out acts of NSSI without suicidal intent. 4.)Through the 5% subset of ALSPAC participants linked with the General Practice Research Database (GPRD) and the recent linkage of ALSPAC to Hospital Episode Statistics, determine the reliability of self-report self-harm and investigate the impact of non-response bias on observed associations. We propose undertaking the following analyses: 1.) Prospective analysis to estimate the incidence of self-harm at age 21. 2.) Prospective analysis based on the self-harm questions at age 11, to identify health and educational impacts of self harm at this age and progression of suicidal thoughts and act between ages 11 and 16. 3.) Prospective analysis based on responders to the self-harm questionnaire at age 16/17. We will assess the impact of self-harm reported at age 16/17 on mental health (CIS-R), educational and other social outcomes by age 18-21. We will compare outcomes for those participants who self-harmed with and without suicidal intent. 4.) We will conduct further prospective analysis to identify social, psychological and educational predictors of self-harm at age 16/17 and 21. 5.) We will explore the reliability of self-report self-harm and investigate the impact of non-response bias on observed associations by identifying a) whether episodes of self-harm identified through HES and GPRD linkage were reported by participants, b) rates of self-harmamongst non-responders to clinics/ questionnaires.
B1214 - Investigation of the correlates and consequences of observed parent-child interactions - 29/07/2011
We propose a series of projects that will be conducted by 5 Clinical Psychology Doctorate students from Exeter University. The projects will all be investigating parent sensitivity during the observed mother-infant interactions at the 12 month Child in Focus Clinic.
Projects 1, 2 & 3: For this proposal we would like to investigate the influence of maternal sensitivity at both 12 months and 61 months on the child's emotional, behavioural and social development looking at early measures of temperament, social cognition and behaviour. In addition ALSPAC provides measures of infant development and temperament at 6 months and therefore before maternal sensitivity was measured. This will allow us to also explore whether an association between maternal sensitivity at 12 months and later infant development is explained by more highly developed or more positively tempered infants evoking more positive maternal behaviour.
Project 4: It is not known whether more sensitive mothers choose to breastfeed or whether the act of breastfeeding impacts on maternal sensitivity. We will be able to further investigate this question by looking at whether it is women's intention to breastfeed during pregnancy or how much they actually breastfed that is associated with maternal sensitivity.
Project 5: In contrast to the wealth of literature on maternal sensitivity very little is known about the nature of father's sensitivity towards their infants. At the child in focus clinic a proportion of fathers brought their infants and participated in the parent-infant interaction instead of mothers. We would compare this to a sample of mother-infant interactions matched on socio-demographic variables from questionnaires administered at different stages. we would investigate whether father's sensitivity is associated with infant developmental measures as is the case for mothers. We will also compare the observed interactions withquestionnaire data on parenting from fathers and mothers.
B1219 - Genetics of prevalent mental disorders in youth testing novel strategies - 29/07/2011
We propose to test three novel approaches to the molecular genetic bases of psychopathology in children and adolescents:
Specific Aim 1: Functional gene group analysis. It is possible to construct polygenic risk scores that account for useful amounts of variance in phenotypes by summing multiple genetic variants of small individual effect. One method that should be particularly helpful in discovering the neurobiological risk mechanisms of psychopathology is to base polygenic risk scores on the many genetic variants that all influence the same cellular function. For the ALSPAC data, functional gene group scores would be created quite easily by running computer algorithms on the existing ALSPAC SNP data.
Specific Aim 2: Hierarchical phenotypes. We may have failed to find strong genetic associations partly because psychopathology phenotypes have not been measured in ways that accurately reflect the nature of genetic risk. Heretofore, we have mostly studied one categorical mental disorder at a time. We propose to use a novel hierarchy of dimensional mental health phenotypes to optimally identify pleiotropic genetic risk variants.
Specific Aim 3: Environmental moderation and sex differences. Testing for gene-environment interactions (GxE) is not a novel strategy, but it is still controversial, greatly underused, and critically important. Therefore, we will test for GxE with prenatal and postnatal environmental variables assessed prospectively to describe their moderation of genetic associations.
B1218 - The relationship between a newly identified functional SNP in the galanin promoter and phenotypic variation in ALSPAC - 29/07/2011
This proposal will study the association of the rs2513280 SNP (which is well imputed in the existing ALSPAC GWAS data set) with a range of phenotypic data from the ALSPAC cohort that relate to metabolism, BMI, lipid profile, addiction, depression and anxiety.
Strategically, we see this as the beginning of an important collaboration of significant translational relevance. In the longer term we will wish to expand the study out to other cohorts available in Bristol, but also into a wider examination of other galanin-dependent phenotypes and/or other genes in the galanin signalling pathway.
B1208 - Effects of early pubertal timing on risk for depression and alcohol use in young women - 28/07/2011
In order to resolve the pubertal status versus timing issue, studies would need to follow girls through puberty to the end to examine whether there are long lasting effects of early puberty on risk for depression.
AIM 1: To examine the association between timing of puberty and depressive symptoms / depression in girls in late adolescence.
AIM 2: To examine the association between early puberty in girls and alcohol use.
AIM 3: To examine the association between depressive symptoms in girls during adolescence and risk for alcohol misuse.
AIM 4: To examine the longer-term impact of early puberty on alcohol use in young women.
We also propose to use recently identified SNPs for early puberty to investigate whether a mendelian randomisation approach will help to determine whether early puberty has a causal relationship with the outcomes.
Outcome variables: Depression, depressive symptoms and alcohol use
Variables that we proposed to examine as potential mediating variables or confounders: Self-image, body image, sexual behaviour, conduct problems, parental supervision, parent-child relationship, IQ, indicators of socioeconomic disadvantage, maternal characteristics (e.g. maternal depression).
B1220 - The Cohorts and Longitudinal Studies Enhancement Resource CLOSER - 28/07/2011
Some of the most important studies of people's lives in the UK, including the University of Bristol Children of the 90s study (ALSPAC), will be brought together in a national centre of excellence thanks to a £5 million project launched this week by the Economic and Social Research Council (ESRC) and the Medical Research Council (MRC).
The Cohorts and Longitudinal Studies Enhancement Resource (CLOSER) project will enable research-ers make better use of the data from nine of the country's leading studies with participants born as early as 1911 and as recently as 2007.
The UK is home to the largest and longest-running longitudinal studies in the world, this world-leading initiative will pay a vital role in maximising the use, value and impact of these studies both within the UK and abroad.
Professor Jane Elliott from the Institute of Education in London will lead a team to establish the na-tional centre of excellence across the nine longitudinal studies. ALSPAC will be represented by its ex-ecutive director, Lynn Molloy and its head of laboratories, Dr Sue Ring.
Strengthening the links between these studies will allow researchers, policymakers and others to make much better use of the rich and detailed data on people's lives gathered over many years in the UK. Repeating the same longitudinal analysis across a number of studies allows researchers to test whether results are robust, and how they are changed by the context in which data has been collected.
Cross-cohort analysis helps the understanding of changes in society and how policy impacts on peo-ple's lives. For example, understanding the background to issues such as the rise in obesity and the stagnation or decline in social mobility requires longitudinal data collected from several generations of people.
A major element of CLOSER will be a single tool that enables researchers to find the information they need for their analyses across all the cohort and longitudinal studies involved. The search platform will be designed for use by a wide range of users with very different levels of experience in data manage-ment, analysis and discovery. It will provide a simple, intuitive interface, encouraging more researchers to use longitudinal data and thereby stimulating interdisciplinary research.
CLOSER will also offer a programme of training which will enable a whole new generation of re-searchers and policymakers to use these rich and complex longitudinal data to help inform key areas such as education and health. It is a £5-million initiative over five years and part of the larger £33.5 million Birth Cohort Facility Project which includes the new birth cohort study - Life Study.
The Universities and Science Minister, David Willetts, said: "Cohort studies give unparalleled insights into people's lives and their life chances. This excellent new facility will make that easier than ever before."
Lynn Molloy, Executive Director of the University of Bristol's ALSPAC, said: "CLOSER is a fantastic opportunity for UK-based cohort studies to work together to better utilize the research arising from these studies. I am delighted that ALSPAC is involved in this groundbreaking project."
Professor Elliott, Director of the Centre for Longitudinal Studies, added: "I am delighted to be given this opportunity to lead this pioneering initiative which will help researchers to address key questions - for example about the factors that are important for children's wellbeing, and about behaviours and experiences that influence health in later life."
B1212 - R-SPONDIN 3 signalling as a link between obesity phenotypes and cardiovascular disease - 21/07/2011
We plan to examine the potential mechanism(s) whereby RSPO3 regulates the functional properties of adipose precursors and thereby regional adipose depot size and function. Manipulation of RSPO3 expression and/or activity to achieve a more beneficial pattern of fat distribution and/or modulate adipose tissue function offers an alternative approach to treat obesity associated cardio-metabolic complications.
To firmly establish the genetic association between RSPO3 and (a) waist-circumference (b) WHR and (c) metabolic profile we seek to genotype the entire OBB and replicate our findings in an independent cohort (mothers of the ALSPAC cohort). In order to achieve this we require ?50 ng of DNA (at 5-10 ng/mcl conc.) to genotype the 3 relevant SNPs. In addition we require anthropometric and biochemical data as described above.
B1191 - Epigenetic marks at birth maternal pre-pregnancy obesity and weight gain during pregnancy - 21/07/2011
We will investigate if maternal overweight/obesity, variation in GWG, and/or gestational diabetes/glycosuria are related to offspring outcomes and if so, whether this correlates with epigenetic changes. One important concern when studying this is the significance residual confounding specially with socio-economic factors. A Mendelian randomization approach can further address the issue of confounding by using genetic variants, reliably associated with adiposity or glucose metabolism, as instrumental variables for its their causal intrauterine effect. For this purpose, we propose to use single nucleotide polymorphisms that have shown strong associations in previous GWAS with adiposity, or fasting glucose. To have the greatest statistical power we will combine the SNPs into at-risk allele scores. As potential offspring outcomes that can be affected by maternal overweight/obesity, GWG and/or gestational diabetes we will select those phenotypes that have been reported to be associated with adiposity during pregnancy including birth outcomes, child adiposity and vascular traits, and respiratory and neurodevelopment phenotypes. We will take into account the effect of potential covariantes. In addition, paternal body mass index will be used as a control. Our main objective will be to investigate the association between maternal overweight/obesity, variation in GWG and/or gestational diabetes/glycosuria with offspring DNA methylation patterns. If evidence of DNA methylation changes in offspring exposed to developmental over-nutrition is found, a secondary objective will be to assess the association between DNA methylation changes with the selected offspring's outcomes. These analyses could reveal potential biological pathways linking the intrauterine environment of over-nutrition with the development of adversephenotypes in offspring later in life.
B1211 - Deriving a measure of maturation status based on percentage of predicted adult stature PhD - 21/07/2011
Background: Pubertal status is an important determinant of many health-related behaviours and outcomes. It is therefore an exposure of interest for numerous outcomes, as well as being a confounder in many exposure. A non-invasive method of assessing maturation status based on the percentage of adult stature (predicted from parental height) that a child has attained has been developed. The percentage of predicted final height for an individual can be compared with age- and sex-specific references to give z-scores, which can then be used to assess the degree to which a child is advanced or delayed in maturation status. The aim of this project is to apply this method to data from participants of the Avon Longitudinal Study of Parents and Children (ALSPAC). Comparison of these measures with other puberty assessments: age of menarche for girls, and for boys and girls, assessments of puberty based on questionnaires in which the child's parent or guardian was asked to identify which line-drawing most closely resembled the child. This method describes 'Tanner'stages ranging between I and V, with I being least sexually mature. Since heights at age 18 are also now available for the ALSPAC cohort, we can compare the predicted final heights with the actual measured heights at age 18.
B1210 - Exploring relationships between facial shape and bone development PhD - 21/07/2011
Background: Rare monogenic disorders such as sclerosteosis have been reported to lead to an increase in bone mass, in association with abnormal facial features such as mandibular overgrowth (1). We have recently observed a similar association in adults identified within the population as having elevated bone mineral density (BMD) (2). More detailed analysis of this cohort of high bone mass subjects revealed increased thickness and circumference of cortical bone, which might conceivably also be related to growth of skull bones. Since facial growth is largely complete by age 15, particularly in girls, analysing associations between indices of face shape obtained in the ALSPAC cohort at age 15, and bone parameters ascertained at the same age, may shed important light on relationships between skeletal development and facial appearance.
Exposure variables: The primary exposure variables will be indices obtained from pQCT of the mid-tibia at age 15, particularly cortical thickness, cortical density, and periosteal circumference. Further exposure variables will include bone measures derived from total body DXA scans performed at the same time, including total body bone area and BMD, and skull area and BMD. Whether bone measures at earlier time points predict subsequent facial features will also be explored, based on total body DXA scans obtained at earlier time points.
Outcome measures: Facial shells, consisting of in excess of 40,000 points, have been generated in 4747 children in ALSPAC at 15 years of age, from which outcome variables for this study have been derived. These comprise 22 distinct facial landmarks, including the relative prominence (z-distance) of the pogonion, nasion and glabella, and thewidth (x-distance) of the chin and bridge of the nose.
B1201 - Pathways to resilience in children born to depressed mothers - 18/07/2011
We have four aims. First, to identify those children born to depressed mothers in the ALSPAC Study who would be classified as resilient on the basis of their scores on the SDQ in middle childhood. Second, to study the factors in early life associated with resilience in this group. Third to investigate the role of quality of early maternal care on development of resilience. Fourth, to identify those early factors involved in resilience which may be potentially amenable to intervention. Specific research questions / study objectives: 1.)When mothers are grouped on severity and duration of depression, what proportion of children born to depressed mothers are classed as resilient on the basis of the median total score on the Strengths and Difficulties Questionnaire (SDQ) administered at ages 8 and 11 by parents and teachers? 2.) Is this concept of resilience generalisable to other outcomes? How do resilient children, non-resilient children, and children of non-depressed mothers compare on other components of adaptive functioning measured when the children were ages 8 to 11 years? Do boys from the resilient group show a different pattern to girls? 3.) How do resilient children compare with non-resilient children and children of non-depressed mothers for the following factors: Exposure to major stressors, Quality of maternal care in the first year, Modifiable factors in the first year e.g. remaining with partner, relationship with partner, parental support, social support, neighbourhood characteristics, financial resources, breastfeeding.4.)Do the modifiable factors in 4 above act through altering the quality of maternal care in the first year or independently? Which aspects of quality of maternal care are important?
B1196 - Prenatal exposure to selenium mercury and lead and childhood atopic and respiratory outcomes - 18/07/2011
Aims: To investigate associations between maternal blood concentrations of selenium, mercury and lead and childhood respiratory and atopic outcomes, and interactions with paracetamol and GST, GCL and GPx polymorphisms. Hypotheses:1) Maternal mercury and lead concentrations in blood in pregnancy are positively associated with atopic outcomes in the offspring.2) Maternal mercury may partly explain the associations of higher socioeconomic status and birth order/parity with childhood atopy.3) Associations with mercury will be modified by GST/GCLC variants in the mother and child, by maternal blood selenium and by paracetamol use in pregnancy. Also, paracetamol effects on asthma and IgE will be modified by mercury exposure.4) Maternal blood concentrations of selenium will be positively associated with wheezing and asthma in the offspring and this relation will be modified by the GPx4 gene variant in mother and child and also by mercury concentrations and by maternal intake of vitamin E.5) A high Hg/Se ratio will be positively associated with atopy; a high Se/Hg ratio will be negatively associated with wheezing and asthma. Primary exposures (data requested): Maternal blood concentrations of Se, Hg and Pb in pregnancy. Outcomes of interest: childhood respiratory and atopic outcomes (data already available). Prenatal and postnatal confounders (data already available).