Proposal summaries
B2441 - A Bayesian mixture framework for epigenetics - 15/05/2015
To further develop a statistical framework to model the epigenetic effects of maternal tobacco smoking on offspring and explore changes in the epigenetic profile over time.
B2442 - Association of mtDNA SNPs with anthropometric and glycemic traits integration with the CHARGEmtDNA consortium - 15/05/2015
a. To perform association of adipose and glycemic traits with mtDNA SNPs in ALSPAC.
b. To perform the association of adipose and glycemic traits with nucmtDNA SNPs in ALSPAC.
c. To meta-analyse the results on all CHARGEmtDNA+ cohorts
B2440 - Are prenatal metabolites nutrients and toxins linked to lung function in adolescence via DNA methylation - 14/05/2015
Are prenatal metabolites, nutrients, and toxins linked to lung function in adolescence via DNA methylation?
B2443 - Methodological toolkit for using digital devices to capture predictive patterns of health behaviours in cohort studies - 14/05/2015
Aims
This project will develop new methods for capturing and analysing health behaviour data from digital devices in cohort studies. It will address specific research questions around identifying patterns of behaviours that predict the start and stop of certain behaviours, including smoking, drinking and snack eating. The underlying methods will be developed in ALSPAC and one other ERSC resourced cohort study (e.g. Understanding Society), and will be designed such they can, through the ESRC's National Centre for Research Methods (NCRM), be adopted by a wider set of cohort studies.
B2439 - Social educational and medical outcomes in young adults on renal replacement therapy in the UK - 08/05/2015
Identify broad social outcomes for young adults on renal replacement therapy
B2437 - Epigenome-wide association study of atopic dermatitis - 07/05/2015
To identify and assess the causal nature of associations between epigenome-wide methylation levels and atopic dermatitis
B2436 - PI-MZ genotype effects on human complex traits including respiratory capacity and height and possible mechanisms - 07/05/2015
PI-MZ genotype: effects on human complex traits including respiratory capacity and height, and possible mechanisms.
B2435 - Methods for dealing with missing data in longitudinal latent class models - 30/04/2015
To establish methods for best practice when dealing with missing data within the context of longitudinal mixture modelling.
B2428 - Youths Resilience and Vulnerability to Maladaptation - 30/04/2015
Aim: To look at the moderating effect of resilience on the effect of neighbourhood deprivation on educational outcomes and externalising problem behaviours.
Resilience is a dynamic developmental process, encompassing the attainment of positive adaptation within the context of adversity (Cicchetti, 2010). Youths with different individual characteristics respond differently to environmental stress, leading either to pathological or resilient developmental outcomes. To explore differences in vulnerability and resilience to environmental adversities, we propose to examine the interaction effects between three important individual psychological and biological characteristics
B2431 - Positive mental wellbeing in emerging adulthood - 23/04/2015
The aim of this project is to collect a battery of positive wellbeing measures in the ALSPAC young adult sample.
B2430 - PARENTAL SEPARATION AS A RISK FACTOR FOR ADOLESCENT DISORDEREDEATING EXPLORING EXPLANATORY MECHANISMS IN A BRITISH COHORT - 23/04/2015
The study will consider the role of several family-related variables in the association between divorce and
disordered eating
B2429 - The fetal childhood and adolescent effects of prenatal exposure to caffeine - 23/04/2015
This proposal is to assess the associations of caffeine intake with outcomes in pregnancy
B2427 - Exploring changes to cardiometabolic risk factors during the menopause - 23/04/2015
To determine the extent to which menopausal age/or chronological age influence cardiometabolic risk factors in women during mid-life (mid-forties to early mid-fifties)
B2426 - The developmental role of Behavioural and Neurobiological Dimensions in predicting Eating Disorders in adolescence/young - 23/04/2015
Eating Disorders (ED) are serious mental health disorders affecting approximately 5-10% of adults (Hudson et al., 2007; Swanson et al., 2011) and have a peak of onset in adolescence between the ages of 15-19 (Micali et al., 2013; Field et al., 2012). The etiology of ED remains poorly understood, though and interplay of genetic and environmental factors is likely to be at play. Research into the clarification of risk factors has been hampered by uncertainties about clear phenotypic distinctions across ED categories, and by a lack of integrative studies using a longitudinal approach to clarify risk for ED. This study aims to focus on how cognitive, emotional and social processes cause ED behaviors in adolescence and young adulthood in interaction with environmental factors from infancy onwards. Cross-sectional studies have identified cognitive, emotional and social difficulties that are associated with ED.
There is cross-sectional evidence that anorexia nervosa (AN) is associated with emotional and social communication difficulties and that specific cognitive profiles characterize bulimic type disorders.AN shares common features with anxiety (Silberg & Bulik, 2005; Micali et al, 2011); and a range of social communication deficits, including interpersonal problems and poor emotion recognition, are present in individuals with AN (Tchanturia et al., 2012; Treasure et al., 2012). Bulimic-type ED are cross-sectionally associated with specific cognitive profiles characterized by poor attention (Dobson & Dozois, 2004; Faunce, 2002) and low inhibition (Galimberti, et al., 2012; Rosval et al., 2006).
Most of the studies cited above are cross-sectional and have often focused on one specific area of behavior or cognition. Large genome-wide studies of psychiatric disorders have highlighted genetic similarities across disorders, indicating either poor specificity of genetic markers or poor specificity of categorical classification systems. The purpose of this study is to investigate the contribution of attention, anxiety and social communication difficulties as well as their biologicla counterparts, genetic data and their interaction with environmental factors to the risk for ED behaviors (restrictive eating, excessive exercise, bingeing, purging at ages 13,14, 16, 18, 24) in a longitudinal developmental fashion.
We propose to use data collected prospectively (and carry out a new wave of data collection) from ALSPAC to investigate the prospective association of anxiety and social communication and AN-type behaviors (restrictive eating and excessive exercise); and cognitive control and attention and BN-type behaviors (bingeing, purging).
B2424 - A Longitudinal Study on the Impact ofStressful Life Events on Obsessive-Compulsive Disorder Symptomatology - 16/04/2015
Logistic regressions will be used to examine the association between stressful life events (SLEs) and OCD symptomatology. Additional logistic regressions will be conducted adjusting for sex, social economic status, depressive symptoms severity obtained from the SDQ at 81 months, maternal depression and marital status.
I will also investigate the impact of missing data using multiple imputation.
B2423 - Team Grant Developmental Origins of Health and Disease - Implications for Men Women Boys and Girls - LOI 2015-04-13 - 16/04/2015
Overview. While fetal exposure to toxic elements has been associated with metabolic disease, and some of these associations are sex-specific, it is unclear if these associations are causal. The overall goal of MET-DETOX is to provide causal evidence as to whether fetal exposure to toxic ele- ments predisposes to type 2 diabetes (T2D) and components of the metabolic syndrome. This will be achieved by identifying maternal and fetal genetic and gene x environmental determinants of toxic elements in fetal cord blood and using this information to undertake Mendelian randomization (MR) studies. Since levels of environmental toxicants are modifiable, understanding their etiologic role could support key public health interventions to decrease the burden of metabolic disease in Canada.
B2422 - Psychosocial stress and eczema persistence - 16/04/2015
The link between psychosocial stress and eczema (aka atopic dermatitis) was identified at least a half-century ago when eczema was designated one the seven classic psychosomatic disorders.[1] The allostatic model of chronic stress proposes that dysregulation of normal homeostatic mechanisms may lead to chronic hyperarousal or hyporesponsiveness.[2] Mechanistic evidence comes from the field of psychoneuroimmunology linking the nervous system, endocrine system, and immune system.[3,4] Stress may also lead to disease-exacerbating behaviors related to diet, sleep, exercise, bathing practices, and treatment adherence.[5] In epidemiologic studies, self-reported stress levels have been shown to correlate with eczema incidence, and stress-reducing modalities have been found to improve eczema symptoms.[6,7]
Various factors are involved in a stress response and will be included in our analyses: exposure to a stressor, resilience/ the use of social supports, and the emotional and behavioral response.[2] We will also include family-related distress such as caregiver stress, maternal panic disorder or depression and family conflict because these have been reported to have immunological effects on younger subjects.[8]
Aim: To examine the association between stress and eczema.
Hypothesis: Higher rates of distressing life events, poor social supports, and psychological distress will each be associated with more persistent eczema.
All patients in the ALSPAC cohort with follow-up data available through age 18 will be included in a longitudinal cohort study. Because the relationship between stress and eczema is likely bidirectional,8 we will model the relationship between each measure of stress and repeated measures of eczema persistence using a marginal structural model and stabilized inverse probability-of-treatment weights to avoid conditioning on stress through its inclusion as a predictor in the outcome model.[9] We will have 90% power to detect an odds ratio as small as 1.23 at a 0.05 significance level in a design with 5 repeated measurements, assuming 15% eczema prevalence.[10,11] We will carefully evaluate missingness and will conduct sensitivity analyses using multiple imputations.[12,13] The results of this study promise to disentangle the individual experience of stress from group-level factors that may be associated with stress including race, socioeconomic status, and environmental factors.
B2421 - Psychosocial Costs of Mens Appearance and Physical Performance-Motivated Behaviors - 16/04/2015
This study relates to a previous (approved) proposal regarding the investigation of eating disorder behaviors in ALSPAC by childhood and adolescent gender expression and adolescent report of sexual orientation. We have additionally proposed the collection for new data concerning current gender expression and sexual orientation, as well as engagement in a wider array of appearance and physical performance-motivated behaviors than has previously been examined in ALSPAC (see accompanying QPF). The collection of new ALSPAC data and analysis of new and existing ALSPAC data will be covered by funding from K01DA034753 (PI: Dr. Calzo) and an R01 from NIH that Dr. Calzo will apply for in October 2015. Analyses of ALPSAC data will complement analyses of data from the Growing Up Today Study and Nurses' Health Study III Men's Cohort in the United States, thus providing a cross-cultural analysis of the comorbidity and costs of appearance and physical performance-motivated behaviors in men's lives from adolescence through middle age.
B2420 - NMR-based Metabolomics pilot on Lymphoblastoid Cell Lines LCLs - a case/control study for Niemann-Pick Type C1 diseas - 16/04/2015
This is a pilot study with the following research aims:
1.) Generation of NMR-based metabolomics data on Niemann-Pick Type C1 (NPC1) disease for identification of metabolic (diagnostic) markers for NPC1 disease at different ages.
2.) Development of methodology to facilitate future work on metabolomics of LCLs.
3.) Evaluation of a 700MHz NMR spectrometer with 1.7mm cryoprobe for metabolomics on mass-limited samples. This instrument is the first of its kind in the UK and offers significant potential for novel metabolomics research. A comparison will be made to data acquired on more standard NMR spectrometers (600MHz with 5mm nitrogen-cooled (Prodigy) probe).
Niemann-Pick type C disease is a complex disorder characterized by elevated cholesterol, glycosphingolipids and sphingosine in endosomal compartments. In the majority of patients lipids are stored due to a defective protein NPC1 a membrane spanning late endosomal protein. A minority (5%) of patients have mutations in a lumenal late endososmal protein NPC2. Although much is known regarding the clinical aspects of NPC disease, the cellular mechanisms leading to neurodegeneration are, to date, poorly understood, and the precise function of the NPC1 and NPC2 proteins remains unknown or speculative. NPC disease has one EMA-approved therapy (Miglustat) which is disease-modifying; however, new, additional therapeutic approaches are urgently required. In order to evaluate these, the identification of novel, clinically-relevant biomarkers for the monitoring of this disease and its progression are necessary.
B2419 - Developing novel online cognitive tests ofspatial perception and memory for use in UK population cohorts - 16/04/2015
We study the potential importance of early life cognitive and brain alterations associated with apolipoprotein (APOE)-?4, an allele linked to increased risk of later life Alzheimer's disease (AD, Genin et al., 2011). With colleagues at Cambridge University, we have recently elicited behavioural differences in young undergraduate APOE-?4 carriers (versus non-carriers) on a novel spatial learning task (Hodgetts et al., in prep). Testing the reliability of this finding, and examination of potential moderators (e.g., gender), now requires larger-scale representative samples. With ALSPAC, therefore, we are writing grants to facilitate new brain imaging and behavioural data collection, as well as analysis of retrospective data. These will address pressing questions about the relationship between early life brain/behavioural changes and later-life cognitive decline.
Here, we propose pilot data collection designed to strengthen a Wellcome Collaboration Award (WCA) between Bristol, Cambridge and Oxford Universities. In the WCA, one key objective is to carry out online data collection using versions of the cognitive paradigms we have established - in smaller scale studies - to be sensitive to APOE-?4 status. This move towards online cognitive tasks (applicable throughout the lifespan and in different cohorts), and large-scale population-level analysis, is new to our research. We do not yet have pilot data that shows, unequivocally, our ability to (a) develop cognitive tasks to enable sensible and robust behavioural assessment and (b) apply these in populations, specifically ALSPAC, underpinning our proposed WCA.