Proposal summaries
B2176 - Characterisation of transgenerational determinants of disease risk induced by ancestral or early-life parental exposures - 20/02/2014
This is part of an EU proposal which will be led by Olle Bygren at the Karolinska Institute in Stockholm. The over-arching aim of the study is to determine transgenerational effects of smoking, stress and famine on subsequent generations. We propose to undertake the following two work-packages using ALSPAC:
1. Transgenerational smoking studies:
Detailed information was collected from the parents during pregnancy concerning their own backgrounds, including their childhood. The details included the age at which the parents started to smoke, the maximum amount they had smoked in their lifetime, the duration in years that they had smoked,and the amounts they were smoking at three stages of the study pregnancy. There was also information on the preceding generation [including whether the parents' own parents were smokers, and whether the grandmother smoked when expecting the study parent]. Information on the study 'child' is now available concerning the age at which he/she started smoking, and the amount smoked in adolescence and will be available for the early 20s.
The data currently available allow detailed time-related data on active and passive smoke exposure of the grandparents, the parents and the child. Although we have carried out research projects on: (a) the association between paternal onset of regular smoking in the pre-puberty [slow growth] period, and (b) exploration of the effects of parental prenatal smoke exposure on the anthropometry of the study children, there is much still to be done.
The long-term effects across the generations of active and passive smoke exposure will be assessed for the first time in a human population. This work-package will determine whether there are other outcomes [we have already shown associations with height, fat and lean mass in the next generation to age 17; these observations will be extended in this work-package to age 24]. Candidate outcomes will include factors that have been linked with smoking in a single generation or with prenatal exposure, but not across generations. Possibilities include: markers of the metabolic syndrome such as insulin resistance, reproductive outcomes such as miscarriage and subfertility; myopia; hyperactivity; conduct disorder and criminal behaviour; neurocognitive and motor development.
2. Transgenerational stress studies:
Detailed information was collected from the parents during pregnancy concerning their own backgrounds, including their childhood. Information included traumatic events, such as separation, divorce or death of a parent, physical or emotional abuse and neglect, with a childhood traumatic life event scale of over 40 items. The parents also completed life event scales to cover the first half of pregnancy, and subsequent approximately annual periods for the first 10 years after delivery. In parallel a series of similar questions elicited traumatic events experienced by the study child at approximately annual periods.
The data currently available allow detailed time-related data on traumatic events to the parents and to the child. Ideally, the study would benefit from knowledge of traumas to the generation before. This work package will be used to make detailed enquiries of the parents in regard to the childhood of their own parents. This would particularly enquire about their experience of World War II - where were they, were they evacuated, were they bombed, did they lose family members as a consequence, etc.
Outcome variables that will be considered include neurocognitive development and motor abilities [we have already shown a strong association between maternal stress in mid-childhood and developmental coordination disorder in the child], as well as growth. We will look in particular at differences between the study offspring according to whether the maternal or paternal parents experienced the trauma, the ages at which it occurred, and the sex of the offspring.
B2175 - AN EXPLORATION OF EXPERIENCE AND ENGAGEMENT IN A BIRTH COHORT/ BIOBANK A QUALITATIVE STUDY - 20/02/2014
AIM:
This study aims to investigate the experiences of participation and engagement of current participants in a longitudinal birth cohort/biobank.
B2207 - Characterising the genetic and dietary predictors of the size frequency and timing of consumption and its health impact - 20/02/2014
Aims: to explore the feasibility of calculating data on the size, timing and frequency of consumption by extracting exact time data from original diet diaries completed at ages 7, 10 and 13 years.
B2174 - Assessing disease by self-report in the 2014 ALSPAC children questionnaire mailout - 20/02/2014
Questions to include:
Have you ever been diagnosed with any of the following?
YES BY A DOCTOR YES BY SELF NO NOT SURE
Asthma
Eczema
Psoriasis
Hypertension (high blood pressure)
Heart Attack/Myocardial Infarction
Stroke
Polycystic Ovary Syndrome
Endometriosis
Crohn's Disease
Ulcerative Colitis
Ankylosing Spondylitis
Psoriatic arthritis
Spondyloarthropathy
Rheumatoid Arthritis
Sjogren's Syndrome
Lupus
Grave's Disease
Multiple Sclerosis
Hashimoto's Thyroiditis
Type 1 Diabetes (Juvenile onset diabetes)
Type 2 Diabetes (Adult onset diabetes)
Schizophrenia
Bipolar Disorder
Depression
Chronic Fatigue Syndrome / ME
Any other diseases/medical conditions (please give details):
B2173 - Hypermobility in young adults - 20/02/2014
Aims
Our over-arching objectives are to further study the basic epidemiology of hypermobility in young adults, and to extend our investigation into the relationship between hypermobility, pain and obesity. Our specific aims are:
1. To produce the first population-based data on the change in prevalence of joint hypermobility between aged 14 and 24. Novel epidemiology of joint hypermobility according to anatomical site, gender, socioeconomics and other basics.
2. To further study the association between hypermobility and pain cross-sectionally (both measured at aged 24) and prospectively (hypermobility at aged 14 with pain at aged 24).
3. To extend the investigation into the associations between hypermobility, pain and obesity by using pQCT measures of fat as well as Mendelian Randomisation (we previously only looked at DXA measures of fat)
4. To investigate the associations between hypermobility and additional symptoms including functional bowel disorders, fatigue and other features of autonomic dysfunction.
B2172 - Investigating epidemiological cognitive and genetic mechanisms underlying the development of psychotic experiences - 20/02/2014
Aims of proposal: The aims of this proposal fall within 3 work themes:
Work theme 1: Epidemiology and environmental risk. We aim to investigate the development of psychotic experiences, at-risk mental states and transition to psychotic disorder from childhood through early adulthood, and examine how social adversity and cannabis use affect these outcomes.
The main questions that we will address in Work theme 1 of this proposal are:
i) What is the prevalence and incidence rate of psychotic experiences, high-risk mental states, and psychotic disorder at age 24 years?
ii) What proportion of those with psychotic experiences or high-risk mental states at age 18 persist, remit, or transition to psychotic disorder at age 24?
iii) How do trajectories of psychosis using data from ages 12, 18 and 24, relate to changes in social and occupational functioning over this time period, independently of time-varying confounders?
iv) What is the effect of a) social adversity, indexed by measures of childhood maltreatment, harsh parenting, peer- or sibling-victimization or disturbed peer relationships, and b) cannabis use, and changes in these exposures over time, on incident psychotic experiences?
Work theme 2: Cognitive vulnerability. We aim to examine whether (i) cognitive models of psychosis based on deficits found in patients with schizophrenia in relation to source monitoring, reasoning bias and predictive coding are associated with psychotic experiences in the general population, and (ii) whether social adversity and cannabis use are associated with these deficits.
The main questions that we will address in Work theme 2 of this proposal are:
i) Are deficits in cognitive processes relating to source-monitoring, reasoning bias, and predictive coding in young adults associated with psychotic experiences at this age, and are these symptom-specific (as hypothesised for source-monitoring (hallucinations) and reasoning bias (delusions))?
ii) To what extent are associations between these cognitive processes and psychotic experiences independent of intellectual ability, adolescent depression, and other potential confounders?
iii) Are experiences of social adversity and cannabis use during adolescence associated with deficits in these cognitive processes, and to what extent might these deficits explain associations between these environmental exposures and psychotic experiences in young adults?
Work theme 3: Genetic risk. We aim to examine whether genetic risk for schizophrenia, based on risk score profiling, is associated with deficits in the cognitive processes described above, and explore how genetic risk for schizophrenia is manifest in relation to neurocognitive, psychopathological, and social phenotypes from childhood through to young adulthood.
The main questions that we will address in Work theme 3 of this proposal are:
i) Does schizophrenia liability as indexed by risk score predict:
* source-monitoring, reasoning bias or predictive coding performance?
* neurocognition (processing speed, working memory, and verbal and performance IQ)?
* psychopathology (psychotic experiences, negative symptoms, depression, anxiety, and autism spectrum disorder traits)?
* social-environmental stressors (social adversity and cannabis use)?
* reduced social and occupational functioning?
ii) Do patterns of association between risk score and neurocognition and psychopathology differ by developmental stage (childhood (0-12), adolescence (13-18), and early adulthood (19-24))?
iii) How does risk of psychotic experiences at age 24 vary in relation to risk score and co-exposure to social adversity or cannabis use?
B2171 - Language acquisition amongst children with dyslexic symptoms - 20/02/2014
Aims: To explore whether children exhibiting dyslexic symptoms related to reading difficulties at 9y differ in their language acquisition during the first 3y compared to children with normal reading abilities.
B2170 - Genetic and non-genetic factors for the early perinatal prediction of coronary artery disease in adulthood - 20/02/2014
Aim: To develop and validate a clinical algorithm integrating genetic and non-genetic (clinical characteristics and cardiovascular imaging) factors for the perinatal prediction of coronary artery disease in adulthood.
B2169 - Thermal injuries in childhood and adolescence - a longitudinal analysis - 20/02/2014
The aim is to investigate longitudinal associations between thermal injuries and various demographic, social, familial and individual factors at different ages throughout childhood. Particular attention will be given to developmental and behavioural child-related exposures on burn outcome at various ages. Burn outcome will be divided into 3 age groups, 0-4.5y, 5-8.5 y and 9-11y. Adolescents will be looked at separately (16y).Children with repeated thermal injuries will be analysed separately.
Our 3 main hypotheses are:
1) Childen with poor coordination and higher scores on hyperactivity, conduct problems and general behavioural problems will be more likely to suffer from burns and scalds.
2) Child factors will be more predictive of thermal injuries compared to family and environmental factors.
3) Thermal injury patterns will vary with age and gender and gender trajectories will change with age. We expect boys to be more likely to suffer from burns during the pre-school period whereas girls will be more likely to suffer at school age when they start to help out with ironing, cooking etc.
B2168 - Investigation of the role of habitual exposure to high impact activity in the attainment of peak bone mass - 20/02/2014
Aims/hypotheses
* We will determine whether habitual exposure to high impacts influences peak bone mass (PBM), by investigating whether these impacts explain the relationship between habitual physical activity and PBM as measured by DXA
* We will examine whether effects of high impacts on PBM translate into greater bone strength, by studying relationships between high impacts and cortical bone strength as assessed by pQCT
* We will determine if a critical time exists in bone development when high impacts exert the greatest long term effects on PBM
* We will investigate whether relationships between exposure to high impacts and PBM represent a causal effect, as opposed to common dependence on intrinsic muscle strength (assessed by jumping mechanography), given physical activity affects muscle strength and muscle strength independently affects bone mass
* We aim to identify whether factors which influence PBM act via altered responsiveness to high impact activity
o We will determine whether individuals with low fat mass show weaker relationships between high impact activity and PBM. Whether such a relationship is explained by altered calorie intake will be investigated, along with the contribution of altered eating behaviour
o We will study whether interactions exist between high impact activity, PBM and constitutive factors affecting cortical bone development eg insulin, adiponectin, bone resorption
* What are the other benefits of high impact exercise for musculoskeletal health? We will investigate whether high impact exercise is associated with musculoskeletal pain, or aspects of hip shape implicated in the pathogenesis of osteoarthritis.
B2167 - Perceptual disturbance of body image as an early risk factor for eating disorders - 14/02/2014
Aims:
1. Investigate factors associated with differences between perceived/actual body size (6.5yrs).
2. Investigate whether such discrepancies predict symptoms of anorexia (14 yrs).
B2165 - The neighbourhood level social and spatial distribution of people with psychotic and affective symptoms at age 18 - 13/02/2014
Aims
This study has five specific aims
1. To describe the prevalence of psychotic and affective symptoms at age 18 years according to neighbourhood-level characteristics at 18-years old, 12-years old, 7 years old and birth using advanced spatial epidemiology
2. To conduct Hierarchical Bayesian Modelling (HBM) to investigate the extent to which psychotic and affective symptoms share a common risk component at the neighbourhood level at each period of the life course
3. To conduct multilevel logistic regression to examine whether duration of exposure to neighbourhood level social disadvantage is associated with the risk of psychotic symptoms at age 18.
4. To examine whether maternal and child-reported perceptions of neighbourhood safety and cohesion are associated with elevated levels of psychotic symptoms, depressive and anxiety symptoms and internalising and externalising disorders in chilhdood
5. To explore the pathways through which exposure to neighbourhood social disadvantage over the life course is associated with psychosis risk, with particularly interest in the mediating role of urban living on the association between individual-level early life adversity, childhood cognitive ability and psychotic symptoms at ages 12 and 18.
B2149 - The lifecourse of the auditory system - 13/02/2014
Aims
1. Characterise the hearing of the cohort from the ages 7 to 14
2. Explore the associations of a range of exposures (physiological, environmental, genetic and epigenetic) with hearing at age 7 to 14
3. Directly assess the hearing of the ALSPAC cohort at age 24
4. Characterise the changes in hearing from age 7 to 24
5. Explore the association of a range of exposures (physiological, environmental, genetic and epigenetic) with the changes in hearing
6. Examine the impact of hearing loss at age 24 on educational outcomes & employment
7. Examine the association of hearing at age 24 with co-morbidities such as visual impairment, mental health, cognitive abilities and precusors to CVD.
B2164 - ALSPAC Epigenomics Strategic Award 2014 - 13/02/2014
Aims
* To enhance ALSPAC to incorporate detailed annotation of epigenomic features and additional epigenomic profiling to provide an internationally leading, widely accessible, population-based reference resource.
To exploit the unique scientific opportunities afforded by ALSPAC to identify epigenetic signatures of exposure, track their persistence over time, across generations and evaluate their relationship with development and disease.
To assess the genetic contribution to DNA methylation variation through leadership of a Genome-Wide Association Study Consortium
To develop a "statistical tool-kit" to facilitate the analysis of population-based epigenetic data
B2163 - Using Mendelian Randomisation to assess causal links between metabolic traits and vascular dysfunction in the young - 13/02/2014
Objectives
Genome-wide association studies (GWAS) have identified genetic variants associated with body mass index (BMI) and blood pressure (BP) in both adults and children (Speliotes 2012, and the International Consortium for Blood Pressure GWAS 2011).
We, at Vascular Physiology Unit, have shown that although greater childhood obesity is associated with adverse metabolic risk factors, there was no evidence of vascular damage by obesity at age 9-11 years in the ALSPAC subjects. Systolic BP was strongly associated with greater adiposity and also increased vascular dysfunction at that age (Charakida 2012). The causal direction and nature of the association between BMI and BP is unclear at this age.
I will investigate the effect of BMI, BP and other metabolic traits on vascular dysfunction ain the young by using a combination of Mendelian randomization and conventional analyses to unravel the complex association between BMI, SBP, metabolic traits and their causal role in vascular dysfunction.
I will be working in collaboration with Kaitlin Wade (PhD student at Bristol) on this project.
B2162 - The role of fathers in the perinatal period positive outcomes and resilience - 13/02/2014
Aims:
In this secondary analysis of the ALSPAC study, we have five aims.
First, we aim to establish what constitutes paternal involvement with the child in the perinatal period. We will be evaluating aspects of the father-infant relationship antenatally, as well as postnatally in terms of attitudes towards parenting, attachment with the child, infant temperament, father's mood and feelings, among others. Second, we will study those aspects of early father involvement that are associated with positive outcomes for the child in terms of scores on the SDQ (*others?). Third, we are interested to know whether the mental health of fathers provides a protective effect to the mental health and wellbeing of the mother. Fourth, we are interested to establish how the quality of the father-mother relationship effects the healthy emotional and behavioural development of the child. Finally, we are looking to identify those early factors involved in positive child outcomes in the father-infant relationship that are amenable to intervention.
B2161 - Applying MR to define risk factors causally related to lung cancer and their potential mediation by DNA methylation - 06/02/2014
Aim:To assess whether the association between modifable risk factors and lung cancer is mediated by DNA methylation.
B2160 - Effects of breastfeeding on childrens cognition the role of DNA methylation - 06/02/2014
Aims: The proposed project aims at investigating the potential mediating role of DNA methylation in the relationship between breastfeeding and children's cognition.
B2159 - Using siblings to understand family process in child behaviour problems - 06/02/2014
Aims:
We propose two linked projects; one addressing sibling, parent-child, and marital interaction quality as predictors of children's strengths and difficulties, and one addressing between- versus within-family risk factors for the development of adolescent antisocial behaviour.
B2158 - Excessive drinking and alcohol related harms in Adulthood ALSPAC at 24 - 06/02/2014
AIMS
We propose repeating the detailed MRI examinations on 125 participants from ALSPAC who were scanned at 18 years as controls for a study of psychotic symptoms (MRC, PLIKS) in order to test the hypothesis that differences in brain structure and dysregulation in function are associated with AU. Thus:-
1. We will compare MR imaging data from their first imaging session (age 18) to the second (age 24) to assess the cumulative impact of drinking alcohol during the intervening years on:
i) brain tissue macrostructure, grey and white matter, using voxel based morphometry (VBM) and cortical thickness measurements
ii) white matter microstructure, including standard diffusion tensor MRI measures (FA, mean diffusivity) and 'hindrance modulated orientational anisotropy', using diffusion MRI (dMRI), and multi-component relaxometry (mcR) to assess putative markers of myelin along specific pathways(52)
iii) activation of prefrontal cortex (PFC) during a task of working memory (n-back).
2. We will investigate whether MR imaging data (VBM, dMRI, mcR, fMRI as above) from the 1st session predicts use of alcohol during the intervening years.
Specifically we hypothesise that compared with those with limited or no drinking, those with greater cumulative alcohol consumption and those predominantly with a binge pattern during the intervening years will show: i) greater reduction in hippocampal, prefrontal, cerebellar volumes; ii) altered WM microstructure in those white matter tracts maturing later (PFC connections eg cingulum, superior longitudinal fasciculus (SLF)) compared with those maturing earlier (eg posterior limb of internal capsule; iii) greater activation during n-back task with unimpaired performance, in their 1st session and when comparing 1st and 2nd sessions.
3. We will investigate the relationship between current and cumulative alcohol consumption with MR imaging data (VBM, dMRI, mcR, fMRI as above) and from ICCAM protocol at the 2nd session, activation of PFC during inhibitory task (go-nogo(53)), activation of ventral striatum during reward task (MIDT(54)), activation of amygdala during stress (stressful images).