Proposal summaries
B2661 - Neurodevelopmental disorders what happens when children grow up and why - 20/04/2016
Neurodevelopmental disorders affect 5% of children and are highly disruptive and impairing; Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) together are the most prevalent and impairing of these disorders in childhood. Previously, affected individuals were thought to "grow out" of such disorders by adult life. However, we now know that is not correct. Longitudinal patient studies show that many manifest high symptom levels and impairment in adult life. However individual developmental trajectories are highly variable and symptom profiles change with maturation. Intriguingly, recent evidence suggests that some forms of adult ADHD emerge without being preceded by a similar childhood phenotype. These findings highlight the need to investigate the natural history of neurodevelopmental disorders into adulthood, in unselected population cohorts. Given the paucity of research on neurodevelopmental disorders and traits at a population level in adulthood, key questions are: 1) what is the longer-term natural history of neurodevelopmental disorders? 2) Do neurodevelopmental disorders originate early in development even when manifest in adult life?
B2655 - Biology and medias Effects And Correlations With Dysfunctional Behavior - 09/12/2016
Thank you for the chance to talk about the Avon data and how it might assist me in my scholarship. If you will take a look at this attached data reference sheet my research assistant and I made, you will see that the data referenced in it (only part of the data) is ideal for studies concerning the relationship between biology, media and crime/justice studies.
B2652 - Two Sample MR of Aspirin Metabolism and Colorectal cancer - 19/04/2016
Colorectal cancer (CRC) is a major public health concern causing the third amount of cancer cases worldwide and is the second leading cause of cancer deaths in the UK and Europe. The survival rates after 5 years of diagnosis is only 50%, even after a gradual improvement over the last 30 years. This indicates a need to try and find effective prevention, diagnosis and treatments for this disease.
One such approach has been to look at commonly used drugs that were not usually considered for cancer use such as aspirin. Aspirin has been shown to be useful for CRC prevention and as an adjuvant to chemotherapy. However, current data suggests that not everyone benefits from aspirin use and this is seen in people who continuously take aspirin but still get colorectal cancer indicating that personalised medicine may be an important aspect of future cancer prevention and treatment.
A summary of the aspirin metabolism pathway has been constructed as well as the metabolites and enzymes involved in the breakdown of aspirin. We have identified candidate SNPs from the GWAS catalogue in the enzymes involved in this pathway and want to verify whether these are associated with levels of different aspirin metabolites.
These genetic instruments will be used in a two sample Mendelian Randomization framework to look at the effect of aspirin intake on colorectal cancer risk.
B2650 - ALSPAC and ELSPAC Pre-birth cohorts with longitudinal data on childhood obesity respiratory development and neurocognitive abi - 13/04/2016
This project is involved with two dimensions of ALSPAC: (a) To enrich the information concerning the maternal environment during pregnancy, and (b) To follow up the ALSPAC participants with questionnaires and a series of hands-on examinations.
(a)In addition to the data already available on the maternal environment, this project will assess the mother’s exposure to the endocrine disruptor bisphenol A; it will enable identification of exposures to infections of the mother (using maternal blood), and the fetus (using cord blood), and allow completion of the obstetric database so that as complete a set as possible of exposures to medications such as pethidine, and interventions such as induction or acceleration of labour, and epidural anaesthesia, can be considered.
(b) The follow up will involve a set of questionnaires to the parents and the index participant at age 27, when detailed questions on the environment over time will be asked, and a clinic slot in 2020 will be used to test hearing, vision, lung function, anthropometry, allergies and various cognitive measures assessing features such as memory, attention span and IQ, as well as collect a number of biological samples.
The project will aim to identify whether the environmental measures are associated with obesity, respiratory and cognitive abilities over time, and in particular what the early childhood indicators of beneficial outcome might be.
B2668 - Investigating the association between parity birth order and self-harm with and without suicidal intent in adolescence - 20/04/2016
A mini project as part of MRC IEU fully funded PhD at Bristol University.
Previous population-based cohort studies have observed higher maternal parity (later born children) to be associated with suicidal behaviour in offspring including suicide and attempted suicide. However, the association between parity and non-suicidal self-harm is less clear, and findings from the few existing studies have been contradictory.The proposed research will examine associations between parity and self-harm with and without suicidal intent amongst adolescents in the Avon Longitudinal Study of Parents and Children (ALSPAC).
B2664 - Associations of smoking with education and neurocognition - 19/04/2016
Smoking is associated with poor educational outcomes, but whether this is due to confounding is hard to tease out. This study aims to investigate smoking during adolescence, and whether this is associated with educational and IQ outcomes (in essence replicating Mokrysz et al's 2016 ALSPAC study on cannabis and educational outcomes but focussing on smoking as the exposure).
As well as this, smoking during pregnancy will also be investigated, to ascertain whether this predicts offspring performance on a neurocognitive task at age 18. In order to attempt to rule out confounding, a negative control design will be used, whereby associations between maternal smoking and offspring neurocognition will be compared to those between paternal smoking during pregnancy and offspring neurocognition, where an intra-uterine effect cannot have occurred.
B2660 - ALSPAC DataSHIELD in the InterConnect Project Subproject1 Physical Activity in Pregnancy Anthropometric Outcomes - 06/04/2016
It has been proposed that additional physical exercise in pregnancy may have a positive impact on birth weight. The development of interventions aimed specifically at increasing physical exercise in pregnancy may therefore produce an important benefit to the health of the public. However, although the effects of such approaches might apply to a very large number of pregnant women and babies across the community, the size of the effect in any one individual is likely to be small. In order to study this properly it has therefore been suggested that a number of large studies should be pulled together in order to determine: (a) is there an effect at all; (b) how large is it; (c) does it matter when the exercise takes place, what form it takes and how extensive it is; (d) are there other factors that modify the impact of physical exercise.
InterConnect is an EU-FP7 funded project that is enabling cross-study analyses to facilitate research to understand the differences in diabetes and obesity between populations, including analyses of gene-environment interaction. At the core of the network is a technology platform for the harmonisation and analysis of data across studies in a manner that avoids the complex ethical and legal issues associated with the physical sharing of data. The investigation that is described above will be one of the initial analyses that will be carried out on the InterConnect platform. It will pull together data from 8 studies including a total of 144,349 participants. ALSPAC is one of the studies that has been invited to be part of the InterConnect consortium. In order to enable the data from all of the involved studies to be effectively analysed together, while ensuring absolute privacy and confidentiality of the data from individual participants, the data analysis will be undertaken using a new software tool called DataSHIELD that has been developed in collaboration with ALSPAC.
B2659 - Exploiting existing biomarker data social position age and allostatic load - 18/04/2016
We are tasked to create a catalogue of biomarker and bio measure data available in the Cohort & Longitudinal Studies Enhancement Resource (CLOSER).
We will describe, compare and analyse bio measures and biomarker data from CLOSER with the objective of measuring Allostatic Load (AL), a quantification of cumulative stress on the body, across the studies with the appropriate data. At present, there is no agreement on methodology to measure AL and no consensus exists as to what biomarkers are essential to calculate AL. We will use past definitions and methods from the literature to calculate AL using the available biomarkers in each of the component CLOSER studies, thus comparing and assessing the usefulness of each definition/methodology. This process will help to develop a gold standard for Allostatic load measurement.
Finally we will examine the association of allostatic load with age and social position within CLOSER.
B2658 - What is the effect of different feeding methods and non-nutritive sucking behaviours on child speech development - 26/01/2017
This project will investigate the relationship between early infant feeding regime (breast/bottle/mixed feeding) and non-nutritive sucking behaviours (dummy/finger-sucking) with speech development at the ages of 2, 3 and 5 years. This will provide information on possible early risk factors for speech sound disorders, which will aid allied health professionals in the early identification and intervention of children requiring support.
The study comprises of 3 strands. The first will examine data from the ALSPAC dataset in three parts. Part A will look at the relationship between infant feeding and parental concern about speech development at age 18 months. Part B will look at the relationship between infant feeding regime and patterns of speech development at ages 25 and 61 months. Part C will look at the relationship between non-nutritive sucking behaviours and patterns of speech development at ages 25 and 61 months. The second strand will use data from the ALSPAC G2 dataset to investigate the relationship between infant feeding regime, non-nutritive sucking behaviours and speech development at the critical ages of 2, 3 and 4 years. The third strand will use data from Speech & Language Therapy clinical caseloads to look at children aged 2, 3 and 4 years with a diagnosis of speech sound disorder (SSD) and their early feeding history and non-nutritive sucking behaviours.
B2656 - Life Cycle - EuroKIDs cohort a Horizon2020 EU application - 07/04/2016
Birth/pregnancy cohorts are studies that recruit mothers during pregnancy or parents and their children at the time the child is first born and collect important health and wellbeing data on them across all of their life, if possible to obtain grant funds to do so. They are very important to understand how where we come from (e.g. what jobs are parents do, which country and city we were born in), what we are exposed to (for example traffic fumes), what we do (e.g. what we eat, how much exercise we do, how well we do at school) and our biological make up (e.g. genetics and epigenetics) act together to influence whether we live a long healthy life, or have health problems and also how well we feel in ourselves and what we go on to do (what job we have as an adult, how many children we have etc.). They are also useful for seeing how large scale things like the global economic crisis can affect health and wellbing.
In Europe there are lots of such cohorts, including the Avon Longitudinal Study of Patents and Children (ALSPAC; also known as Children of the 90s), which is considered to be one of the best of these types of studies. Each of these studies alone have increased our knowledge of what causes some people to be well and others not and what things are important for general wellbeing. But together they can achieve a lot more. We want to bring these cohorts together in order to better understand how what happens to us when we are in the uterus (when our mothers are pregnant) and what happens to us at birth and early childhood influences how we grow, how fat or thin we are, whether we have risk factors for heart disease, diabetes, asthma or other breathing problem, depression, schizophrenia or other mental health problems. By putting all of these cohorts together we will also be able to determine what early life risk factors affect getting diseases in later adulthood.
B2651 - Improvements in Maternal Health Behaviors and Conditions Increase Twinning - 04/04/2016
We examine whether mothers with greater health stocks and mothers who behave in a healthier manner during pregnancy are more likely to give live birth to twins. We have collected a number of microdata sets from various sources and countries, and in each case are collating variables measuring mother's health outcomes or behaviours, as well as whether the mother has ever given birth to twins. Using a number of statistical tests, we will examine whether those mothers who give birth to twins look different to mothers who don't give birth to twins, and if so, whether twins are more likely to occur when mothers have greater health endowments.
B2647 - Cognition as a protective factor in the presence of elevated genetic and environmental risk factors for psychiatric disorder - 01/07/2016
It is well established that many common adult psychological difficulties have their origins in childhood and adolescence (Kim-Cohen et al., 2003). It is also known that the causes of psychological difficulties such as anxiety, depression, psychosis and attention deficit hyperactivity disorder include both inherited and environmental factors. For instance, stressful life events such as being victimised by peers or losing a loved one increase the risk of experiencing psychological difficulties. Similarly, molecular genetic studies have identified genetic variants that have a small but significant effect on the likelihood of developing common psychological disorders. Better cognitive ability and planning appear to protect individuals from developing psychological problems. This may be because better cognitive processing enables individuals to ‘cope’ more effectively with genetic and environmental risk by allowing them to employ compensatory strategies. Several recent studies support the view that cognitive ability may protect individuals from developing problems when they have either genetic or environmental risk factors (Kendler et al., 2014; Johnson, 2012; Davidovich et al., in press; Pargas et al., 2008; Riglin et al., 2016). In this study, we aim to examine whether cognitive ability and executive functioning protect individuals against developing psychological problems when they are exposed to environmental or genetic risk.
B2646 - Applying Mendelian randomization to predicting the overall effects of interventions targeting sclerostin - 14/03/2016
Studies of the associations of circulating sclerostin levels with a variety of outcomes have been inconclusive, although there have been reports of associations with a variety of conditions. It is unclear with such associations, however, whether these findings represent causal effects of sclerostin, or confounding. Mendelian randomization offers an approach to estimating causal effects in the presence of such confounding.
Once common variants robustly associated with serum sclerostin levels are detected it is possible to apply two-sample Mendelian randomization analyses to predict the effect of influencing serum sclerostin on a very wide range of outcomes, utilising the available GWAS data from a large number of conditions that could be influenced by serum sclerostin modification.
Requirements for a comprehensive investigation applying this approach to sclerostin would be (1) assaying sclerostin on a large sample of GWAS’d study participants to produce reliable data of genetic associations with serum sclerostin, (2) performing two-sample Mendelian randomization analyses predicting the effect of modifying sclerostin on a wide variety of health-related outcomes (see appendix for a summary of accessible resources), (3) within single large samples with particularly informative phenotyping (such as ALSPAC and UK Biobank) performing a detailed analysis of the predicted effects of modifying sclerostin.
These data would then provide powerful GWAS assessment of genetic associations with sclerostin as well as the basis for a comprehensive investigation of the association of sclerostin with a wide range pf phenotypes. In addition, factors (e.g. obesity) that may influence sclerostin can also be investigated within both the conventional and MR frameworks.
B2641 - Longitudinal trajectory clustering allowing for genotype effects - 07/06/2016
We propose to compare different statistical approaches to working with longitudinal trajectory data in the context where there are different time points when individuals are measured as well as variable missing data patterns. In particular, we want to look at the power for detecting genotype effects on trajectories.
B2630 - common variants causing intellectual disability - 15/03/2016
neorological development information such as IQ score
B2645 - Adverse life events inflammation and trajectories of emotional and behavioural problems in childhood - 09/03/2016
Much research has linked adverse life events, a widely-used measure of stress, to the aetiology and maintenance of emotional and behavioural problems in children. Stress can initiate biological processes that increase risk for both types of problems in children but no study has yet examined inflammation as the stress-induced biological process that can increase this risk. Inflammation is typically thought of as the body’s primary response to physical injury or infection. However, there is now substantial evidence that stress can also trigger significant increases in inflammatory activity which may account for how external stressors ‘get under the skin’. Increases in inflammation can in turn elicit profound changes in behaviour, which include the initiation of symptoms such as sad mood, anhedonia, fatigue and social and behavioural withdrawal. This project will examine, for the first time, the role of stress-induced inflammation in childhood in the aetiology and maintenance of emotional and behavioural problems from childhood to adolescence. This is the main aim of this project, which we will meet using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK study of more than 14,000 pregnant women in 1991-2, the children arising from the pregnancy, and their partners. Adverse life events will be measured at both the prenatal and the childhood period, in view of the evidence that prenatal and childhood adversity can affect children through different mechanisms. We will also explore the complex ways in which events may interact to predict child outcomes, investigate the importance of distinguishing events by type (e.g., dependent vs independent; chronic vs episodic), and examine the role of their perceived impact. Emotional and behavioural problems will be measured with the Strengths and Difficulties Questionnaire (SDQ) at ages around 4, 7, 8, 9, 12, 13 and 16 years. In ALSPAC, inflammation in childhood was measured at age around 9 years with levels of interleukin 6 and C-reactive protein.
Our analyses will consider two important issues. First, that inflammation can be caused by a number of factors. Therefore, we will control for a diverse range of health-risk behaviours (e.g., poor diet, lack of exercise, sleep disturbance) and environmental challenges (e.g., low socio-economic status), as these can also activate inflammation, and we will exclude a small number of children with an infection at the time inflammation was measured. Second, that causal associations between inflammation, stress and emotional/behavioural problems may be complex. For example, inflammation in children has been implicated as both the outcome of stress and the outcome of emotional or behavioural problems. Thus we will also explore:
i. the role of adverse life events in inflammation. For this part of the project, we will focus on adverse life events preceding the measurement of inflammation (that is, events that occurred at the prenatal period and at ages around 0-9 years), and
ii. the role of emotional/behavioural problems in inflammation. For this part of the project, we will focus on emotional/behavioural problems preceding the measurement of inflammation (that is, at ages around 4-9 years).
There is another, related, objective: to examine the reciprocal nature of the influences between adverse life events and emotional/behavioural problems. Adverse life events can be the cause but also the outcome of such problems. We will be able to examine the direction of this association using a subset of adverse life events, namely those that were measured repeatedly and at the time emotional/behavioural problems were assessed. This will enable us to test two competing hypotheses of the role of inflammation in the longitudinal link between adverse life events and emotional/behavioural problems in childhood. That is, that a) problems cause inflammation, leading to life events, or b) life events cause inflammation, leading to problems.
B2644 - Early life respiratory tract infections and lung function/asthma - 09/03/2016
Respiratory tract infections in early life (that is, before school age) might lead to lower lung function, and have an effect on the development of asthma. By using data of various European studies that have data on these variables, we hope to examine these effects.
B2643 - Evaluating GREML to Estimate Heritability due to Parent of Origin Effects - 09/03/2016
We have recently developed a statistical method which relates the differences in traits across people to the patterns of genetic variants that have been inherited from each parent.The goal of this approach is to identify traits in which maternal (paternal) inheritance has as a subtle effect at many locations in the genome, and, when this occurs, to estimate the overall strength of this effect.
To evaluate the usefulness of this method, we hope to apply it to several traits. Most importantly, we plan to apply it to age at menarche, a trait for which there is some evidence that maternal inheritance has as a subtle effect at many locations in the genome. Additionally, we plan to apply the method to other traits which we have experience studying and which are well characterised in the literature, so that we can make informed comparisons between results from our method and from published work. For these comparisons, we plan to use traits related to bone health, as well as measurements of reaction time.
B2642 - Parenting practices in association with ADHD and adolescent outcomes - 14/03/2016
Childhood maltreatment is a prevalent risk factor associated with long-term morbidity and mortality, mental health problems, and adult violence[1-2]. In 2014 alone, 6.6 million children in the U.S. were involved in referrals where there was alleged maltreatment, including 702,000 victims of child abuse and neglect[3]. Psychiatric morbidity attributed to early maltreatment is extensive and often severe[4-6]. Recent research reveals associations between adverse childhood experiences including physical abuse and neglect with ADHD[7-8]. ADHD is a psychiatric disorder with childhood onset (<12), characterised by its dimensions of hyperactivity/impulsivity and inattentiveness[9], and its high heritability is well documented[10]. ADHD is also associated with problems related to executive functioning, including the ability to self-regulate[11].
Quality of parental care, including harsh parenting is a risk factor for the development of behavioural problems early in life[12]. Parenting and family factors have been recognised to affect the course of ADHD, and the development of comorbidity. In addition, parents of children with ADHD report significantly more stressful and dysfunctional parent-child interactions than do parents of children without ADHD[13].
Studies examining the relationship between ADHD and maltreatment have reported significant associations[7-8, 14-15], however most of these studies have used cross-sectional designs, limiting any directional or causal interpretation. Most also lack essential confounders such as family-level and psychiatric factors, and unexplained genetic variance. Early maltreatment as a distinct risk factor for ADHD has not been effectively examined. Moreover, the role of parenting behaviours and early maltreatment with ADHD has not been systematically studied using well-characterised population data.
Our aim is to the examine the role of parenting practices, with an emphasis on maladaptive parenting and early child abuse, with the developmental course of ADHD symptoms and its symptom trajectories from early childhood through adolescence, and associated adverse outcomes. We aim to perform a systematic evaluation of the role of these exposures at the population level using representative longitudinal data.
1. Gilbert R et al. Burden and consequences of child maltreatment in high-income countries. Lancet. Jan 3 2009;373(9657):68-81.
2. Gonzalez RA et al. Childhood maltreatment and violence: Mediation through psychiatric morbidity. Child Abuse Negl. Jan 21 2016;52:70-84.
3. U.S. Department of Health & Human Services AfCaF, Administration on Children, Youth and Families, Children’s Bureau., ed2016. Child Maltreatment 2014.
4. Horwitz AV et al. The impact of childhood abuse and neglect on adult mental health: a prospective study. J Health Soc Behav. Jun 2001;42(2):184-201.
5. Johnson JG et al. Childhood maltreatment increases risk for personality disorders during early adulthood. Arch Gen Psychiatry. Jul 1999;56(7):600-606.
6. Bebbington P et al. Childhood sexual abuse and psychosis: data from a cross-sectional national psychiatric survey. Br J Psychiatry. Jul 2011;199(1):29-37.
7. Fuller-Thomson E et al. The relationship between early adversities and attention-deficit/hyperactivity disorder. Child Abuse Negl. Apr 3 2015.
8. Guendelman MD, Owens EB, Galan C, Gard A, Hinshaw SP. Early-adult correlates of maltreatment in girls with attention-deficit/hyperactivity disorder: Increased risk for internalizing symptoms and suicidality. Dev Psychopathol. Feb 27 2015:1-14.
9. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: Author; 2013.
10. Thapar A et al. The genetics of attention deficit hyperactivity disorder. Hum Mol Genet. Oct 15 2005;14 Spec No. 2:R275-282.
11. Velez-Pastrana MC, Gonzalez RA et al. Psychometric Properties of the Barkley Deficits in Executive Functioning Scale: A Spanish-Language Version in a Community Sample of Puerto Rican Adults. Psychol Assess 2015.
12. Miner J et al. Trajectories of externalizing behaviour from age 2 to age 9: Relations with gender, temperament, ethnicity, parenting and rater. Developmental Psychology. 2008; 44(3): 771-86.
13. Briscoe-Smith AM et al. Linkages between child abuse and attention-deficit/hyperactivity disorder in girls: behavioral and social correlates. Child Abuse Negl. Nov 2006;30(11):1239-1255.
14. Linares LO et al. The course of inattention and hyperactivity/impulsivity symptoms after foster placement. Pediatrics. 2010;125(3):e489-e498.
15. Ouyang L et al. Attention-deficit/hyperactivity disorder symptoms and child maltreatment: A population-based study. The Journal of Pediatrics. 2008;153(6):851-856.
B2621 - Association of childhood mental health with adolescent substance abuse - 26/05/2016
‘Social cognition’ refers to multiple psychological processes underlying human interaction, including understanding that other individuals are also experiencing complex emotions (known as ‘Theory of Mind’), and the ability to recognise these emotions (for example, through facial expressions). Long-term drug users often have problems with social cognition. Users of cannabis, tobacco, alcohol, and other drugs have difficulties recognising others’ emotional expressions, and have difficulty understanding with Theory of Mind. However, it’s not clear if using drugs results in these problems, or if people who have poor social cognition to begin with are more prone to use drugs. For example, people with poor social cognition may use drugs to improve their interactions with others. The use of drugs to help with a psychological problem is known as ‘self-medication’, and there is some evidence for this. For example, heavy smokers only seem to have difficulty with social cognition when they stop smoking. Additionally, many individuals’ suffering from mental health problems believe that their drug use helps to alleviate their symptoms (for example, by reducing their anxiety). Many mental health disorders also include problems with social cognition and are linked to high rates of drug dependence. For this reason, we previously studied the relationship of poor social cognition in childhood (age 7) with teenage drug use (age 17). Interestingly, we found that poor social cognition in childhood (particularly recognising emotional expression) was related to decreased teenage drug use. The current study aims to explore the relationship between childhood mental health problems (age 7) and teenage drug use (age 17). By examining childhood mental health problems separately from social cognition, we can explore if these two are related to teenage drug use in similar or different ways. Our results may be useful for identification of targets for early intervention.