Proposal summaries
B2717 - DNA methylation characteristics in cord blood after paracetamol exposure during pregnancy - 22/07/2016
Paracetamol (Acetaminophen) is a common “over-the-counter” NSAID, which is commonly regarded as safe when taken in in recommended doses. The most common side effects of paracetamol over-use is acute liver failure.
New large epidemiological studies suggest that there may be second generation effects when paracetamol is taken by the mother during pregnancy. The current evidence have linked maternal pregnancy exposure of paracetamol to increased risk of ADHD (ADD) and wheeze/asthma in the children. We aim to explore the effect of maternal paracetamol intake during pregnancy on DNA methylation in offspring at birth. This project forms part of a collaboration where test statistics will be used in meta-analysis with additional cohorts.
B2716 - Impact of dietary xanthine consumption on myopia in mothers and children from the ALSPAC Cohort - 14/07/2016
The current generation of school students and young adults are destined to be significantly more short-sighted (myopic) than their parents. Several possible treatments to slow down the development of short-sightedness (myopia) have been identified by scientists. One of these (7-methylxanthine), taken as a tablet, is closely related to both caffeine, which is found in many drinks, e.g., Coca-Cola, as well as in tea and coffee, and another chemical that is found in chocolate. We have little information about how effective these other chemicals might be in treating myopia, but most of us eat or drink something containing these chemicals everyday. This project is designed to see if caffeinated drinks and/or chocolate might protect us to some degree from developing myopia. If we find this effect, this result may help us develop new ways of treating myopia.
B2713 - Mendelian randomization for metabolites on coronary heart disease and Type 2 Diabetes - 14/07/2016
Utilizing the metabolomics data in ALSPAC and GWAS summary-level data in MR-base to understand the relationship between circulating metabolites on coronary heart disease and Type 2 diabetes and try to solve the issue of pleiotropy with the lipid variables.
B2712 - The migration history of Bristol seen through a UK Breakdown of Ancestry decomposition for the ALSPAC cohort - 06/07/2016
Based on methodology developed at the University of Bristol, it is now possible to identify the geographical region of the ancestors of an individual at the World, European, and importantly, at the UK county scale, based on genetic data that has already been gathered on the ALSPAC participants. This project will feed this personalised ancestry information back to the participants, and produce both a scientific and a lay summary of the overall ancestry of Bristol.
B2711 - The association between psychological symptoms and the onset of musculoskeletal pain - 19/07/2016
Musculoskeletal (MSK) pain is a major concern worldwide and it is common in adults as well as children and adolescents. Currently, research suggests that many adults who report pain actually have pain that persists and remains stable over time. However, what we don’t know yet is at what point these long term patterns of pain begin, although some emerging research suggests that pain events in childhood may be the starting point of long-term pain problems in adulthood. A recent systematic review was conducted by the authors of this data request (write up in progress) to look at factors that appear to increase the risk of musculoskeletal pain in children. Our findings show that psychosocial factors (e.g. anxiety, depression, behaviour problems) increased risk of musculoskeletal pain onset. However, our review does not tell us how these factors have an effect or the way psychosocial factors lead to a child or adolescent having musculoskeletal pain. The ALSPAC cohort offers a unique opportunity to investigate the relationships between psychological symptoms and the onset of MSK pain, as outlined above, this research will help to give a better understanding to what factors increase the risk of musculoskeletal pain in children, and importantly how. We will also be able to investigate whether the amount of screen time, pubertal stage and gender affects this relationship. Finally, we will look at whether our findings are different when we take factors such as sleep problems and substance abuse into account through our analyses.
B2706 - Interplay between Peer-based Processes and Alcohol Metabolism Genes on Trajectories of Alcohol Use across Adolescence - 12/07/2017
Underage drinking is a highly prevalent and serious public health concern. Up to 20% of high school students report binge drinking in the past two weeks, and underage drinking can result in significant short- and long-term consequences (e.g., drunk driving, academic/occupational impairment, later alcohol and substance use disorder). While alcohol use on average increases over the course of adolescence and decreases during the transition to adulthood, research has identified several distinct trajectories of alcohol use across development. These distinct trajectories have different prognoses for long-term outcomes (e.g., later alcohol and substance use disorders), highlighting the need to identify the person and environmental determinants of high-risk pathways to inform prevention efforts for young drinkers.
According to an interactional perspective, there are dynamic, reciprocal interactions between person and environmental factors across development. In regards to alcohol use, it is well documented that adolescents both match their peers’ drinking (i.e., peer socialization) and seek out peers compatible with their own alcohol use (i.e., peer selection). Emerging, albeit limited, evidence suggests peer socialization and selection processes may be modulated by genetics. Variations in alcohol metabolism genes (i.e., ADH and ALDH) have been consistently found to influence drinking behavior, with high-activity variants protective against alcohol use/misuse. These protective effects may attenuate peer socialization and selection processes, with adolescent high-activity carriers less likely to associate with and less susceptible to alcohol-promoting peers. The proposed project would be the first to examine moderation of peer socialization and selection processes by alcohol metabolism genes within adolescent drinking trajectories.
B2705 - Cohort Studies resources for investigating health outcomes using environmental data - 03/05/2017
Cohort studies provide an ideal resource for the investigation of how the exposures people receive from the natural environment (for example, the pollutants in the air we breath) effect our health and development. This is the case as cohorts collect large volumes of information about a group of people over long periods of time (enough time for environmental exposures to manifest themselves in health/development outcomes), while maintaining records of where people live (attend school, work etc) during this time. However, the potential for this type of research is limited for three main reasons: 1) typically historical environmental data are difficult to locate and interpret; 2) cohort data managers are unfamiliar with the techniques needed to link environmental records to their participants; 3) there are concerns that using geo-spatial data (e.g. postcode) may reveal participants identity and risk the confidentiality of the information they have provided to the study. This feasibility project will look to address these three limitations by: 1) cataloguing the available data; 2) conducting exemplar linkage projects to refine and document linkage techniques, and 3) assess the disclosure risk present in this type of research and to implement effective measures to deal with these risks. The exemplar research will investigate the impact of air pollution (specifically NOx) on lung function and, separately, the impact of living in proximity of a crematoria on maternal blood mercury levels in pregnancy.
B2710 - Imputation of ALSPAC Fathers and ReImputation of ALSPAC Mothers and Children - 01/07/2016
ALSPAC has contributed to a large number of genomewide association studies (GWAS). We have these data imputed to the recent reference panels for 9321 mothers and 9115 children (1000 genomes). We currently also have Fathers data, which is yet to be imputed and therefore cannot be used as effectively as possible (for example a typical contribution to a GWAS consortium requires imputed data). Furthermore our current imputations need to be continually updated as new opportunities arise and re-imputation with the latest available 1000 Genomes panel is necessary to continue contributing to large meta-analyses.
B2709 - Do maternal B-12 and Folate intake independently predict birthweight childhood obesity and cardiovascular risk in adolescents i - 04/05/2017
Obesity, leading to diseases such as diabetes and ultimately cardiovascular disease is an important public health issue. The current environment has been called “obesogenic” that is, it makes it easy for us to adopt a lifestyle of over-consumption of calories alongside low physical activity, increasing the risk of obesity. However, while lifestyle factors are undoubtedly important, there is evidence that an individual’s risk of obesity and associated diseases can be “programmed” in the womb. Specifically, if a woman is undernourished while pregnant, her baby may be born smaller than usual and have increased risk of Type II diabetes and cardiovascular disease (heart disease and stroke) as an adult.
Epidemiological studies have shown an association between low vitamin B12 intake in pregnant women and low birth weight babies, who goes on to have more ‘bad’ than ‘good’ fats in their blood, higher BMI, higher heart rate and greater risk of insulin resistance (pre-diabetes) as children. In addition, three studies in Indian populations suggest high folate intake, by mothers who have low intake of vitamin B12, is associated with low birth weight babies and increased fat mass and insulin resistance in those babies in childhood. This suggests the hypothesis that a pregnant woman’s dietary intake of vitamin B12, and the ratio of B12 to folate may influence her baby’s birthweight and risk of obesity, diabetes and cardiovascular disease when they grow up. We plan to investigate this hypothesis using the Avon Longitudinal Study of Parents and Children (ALSPAC).
ALSPAC has documented the health of 14,500 families in the Bristol area since 1990. Pregnant women were recruited into the study if their baby was due between April 1991 and December 1992. Detailed information has been collected on these women and their families using questionnaires, data extraction from routine information systems and research clinic visits. Information on folate and vitamin B12 intake in pregnancy (our “exposures of interest”) will come from a food frequency questionnaire completed by 10,851 women when they were 32 weeks pregnant, as well as questions on supplementation at 18 and 32 weeks of pregnancy.
We will examine three outcomes: 1. Birthweight: using information on birthweight and gestational age recorded from routine hospital data systems. 2. Childhood obesity: using height, weight and waist circumference measurements made at clinic visits when the child was 7, 11 and 16 years old. 3. Cardiovascular disease risk: we will examine a) the profile of fats in a blood sample taken when children were 15 years old, including total cholesterol, triglycerides, HDLc and LDLc, b) a measure of insulin resistance using blood glucose and insulin concentrations, and c) blood pressure recorded at the same clinic visit. These data are available in existing datasets.
We will use sophisticated statistical methods (Bayesian network analysis) to examine the association between our exposures of interest and the identified outcomes with adjustment for possible confounding factors such as socio-economic status and mother’s BMI. These methods will also account for the relationships between the outcomes in a way that has not been examined previously.
Our findings will be important because current advice to pregnant women recommends supplementation of their diet with folic acid. It may be that this should be updated to include a B12 supplement in women at risk of low intake of this vitamin (such as vegetarians). In addition, in some countries there is mandatory fortification of cereals with folate. If this results in a low ratio of B12 to folate in the general population, fortification may exacerbate the problem of childhood obesity, increase prevalence of diabetes and increase cardiovascular risk. Although our analysis will not provide a final answer to the question of whether there is a causal link between intake of these nutrients and risk of the conditions examined, it will suggest whether further research into this issue is worthwhile.
B2708 - Linking medical and geo informatics to study harmful elements in soils - 01/07/2016
Potentially harmful elements (PHE) in the environment, either derived from natural or man-made sources, are known to have impacts on human health. The British Geological Survey’s Geochemical Baseline Survey of the Environment (GBASE) quantifies the concentrations of some 50 elements in soils across the UK. BGS’s medical geologists have studied how much of these contaminants are available for absorption into the systemic circulation of the human body through different exposure routes. There is, however, a lack of information on the relationship between the concentrations of the PHEs in soil in a specified area and the concentration of the PHE in humans living in the same location. In order to obtain this information detailed studies of the body burdens of PHEs in human subjects (as measured by human biomarkers, e.g. blood, urine, finger/toenails and hair) is required alongside of high resolution geochemical sampling of the local soils.
This information will provide medical practitioners and risk assessors with the necessary information required to assess what concentration of PHE in soil constitutes a safe level.
B2703 - Genome-wide polygenic scores for cognitive abilities - 28/06/2016
Cognitive abilities are the best behavioural predictors of key societal outcomes and among the most heritable behavioural traits. Attempts to identify genes associated with cognitive abilities have been hindered by the expense of assessing them in large samples. The goal of the proposed research is to add standardised web- and mobile app-based cognitive measures to large international biobanks that already have genetic data for large samples.
B2704 - Dietary patterns essential fatty acid status self-harm amongst adolescents - 28/06/2016
Summary
The aim of this work is to determine if dietary patterns, specific foods, nutrients, or essential fatty acid plasma status are associated with an increased or decreased risk of self-harm behaviors amongst adolescents. We ask this question because i) the importance of nutrients and psychiatric function is being increasingly recognized and ii) if dietary patterns, specific foods, nutrients or essential fatty acid are identified as a significant risk factor, then these findings can potentially be translated to public health benefits. Finally, we do not propose that diet patterns, specific foods, nutrients or essential fatty acid are sole cause determinants of self-harm risk, but are to be evaluated as possible modifiable risk factors.
Risk Factors and Treatment of Self-Harm
Previous literature indicates that deliberate self-harm is often predicted by a stressful event, such as child abuse, early history of hospitalization or medical treatment, parental separation, etc. (Briere & Gil, 1998; Favazza & Rosenthal, 1993; Fliege et al., 2009). According to Greydanus et al.(2006), deliberate self-harm may occur in attempt to relieve “a terrible state of mind” in those engaged in such behavior. For example, self-cutting behavior often serves as a way to release unbearable pain from suppressed negative feelings driven by underlying depression and anxiety from conflicts with family and/or peers (Greyandus et al., 2006; Nixon & Jansson, 2002). Furthermore, repeated studies have found depression, history of sexual abuse, exposure to self-harm, and concerns about sexual orientation to be main predictors of repeating deliberate self-harm acts (Nixon & Jansson, 2002; Goldman-Mellor et al., 2014). Despite increased awareness and knowledge regarding the importance of deliberate self-harm, there remains a lack of consensus over how it should be assessed and treated.
Diet, Dietary Patterns and Mental Health Outcomes
Nutritional quality and dietary patterns are becoming increasingly recognized as important factors in the prevalence and incidence and treatment of mental disorders (Sarris et al., 2015). Many epidemiological studies, including prospective studies, have shown associations between healthy dietary patterns and reduced prevalence and risk for depression (Lai et al., 2014; Psaltopoulou et al., 2013). In particular, a traditional whole-food diet, consisting of higher intakes of foods such as vegetables, fruits, seafood, whole grains, lean meat, nuts, and legumes, with avoidance of processed foods, is more likely to provide the nutrients that afford resiliency against the pathogenesis of mental disorders (Sarris et al., 2015). Studies have also reported a relationship between “unhealthy” dietary patterns and poorer mental health outcomes in children and adolescents (O’Neil et al., 2014). Poor diets consisting of high amounts of fat and sugar are associated with adverse mental health outcomes (O’Neil et al., 2014). Evidence is steadily growing for the select use of nutrient-based supplements as monotherapies or augmentation therapies to address mental health outcomes (Rucklidge et al., 2013). Multiple studies report that omega-3 fatty acid supplementation (in isolation, or in combination) is beneficial in the management of bipolar depression, post-traumatic stress disorder, and major depression; and is indicated in the prevention of psychosis (Mischoulon & Freeman, 2013, Hallahan et al 2016).
Here we propose to extend the examination of dietary patterns, specific foods, and specific nutrients to risk of self-harm and suicide risk factors. Only one study has reported associations between “prudent “Japanese dietary patterns (i.e., vegetables, mushrooms, fish, and seaweed) and lower risk of suicide mortality (OR 0.46, 95% CI 0.28–0.75, p<0.005) (Nanri et al., 2013). To our knowledge, no studies have examined relationships between dietary patterns specific foods and deliberate self-harm. Data from epidemiological studies have also indicated that low fish consumption may be a risk factor for suicide mortality. For example, one longitudinal study followed up 256,118 Japanese participants for 17 years; those who ate fish daily had a lower risk of death from suicide (OR 0.81; 95% CI 0.27–0.91) compared to participants eating fish less than daily (Hirayama, 1990; Karger, 1990). Another study in Northern Finland examined data from 1,767 participants and found that frequent fish consumption significantly reduced the risk of depressive symptoms (OR = 0.63; p < 0.03) and suicidal thinking (OR = 0.57; p < 0.04) after adjustment for confounding variables (Tanskanen et al., 2001). Blood compositional studies have reported that low omega-3 status is associated with greater risk of suicide death amongst US Military personnel (Lewis et al., 2011); in Belgian patients (De Vriese et al., 2004); and amongst Chinese subjects with suicide attempts (Huan et al, 2004). One randomized controlled trial of emergency room patients with deliberate self-harm found that 2 grams/day of omega-3 supplementation reduced suicidal thinking by 45%, depressive symptoms by 50%, perceived by 30%, and increased reports of happiness by 33% (Hallahan et al., 2007). Lastly, omega-3 fatty acid supplementation is currently being examined for US Military veterans at risk for suicide (Marriott et al., 2016).
References
Briere, J., & Gil, E. (1998). Self-mutilation in clinical and general population samples: prevalence, correlates, and functions. American journal of Orthopsychiatry, 68(4), 609.
De Vriese SR, Christophe AB, Maes M: In humans, the seasonal variation in polyunsaturated fatty acids is related to the seasonal variation in violent suicide and serotonergic markers of violent suicide. Prostaglandins Leukotr Essent Fatty Acids 2004; 71(1): 13–18.
Evans, E., Hawton, K., & Rodham, K. (2005). In what ways are adolescents who engage in self-harm or experience thoughts of self-harm different in terms of help-seeking, communication and coping strategies?. Journal of adolescence, 28(4), 573-587.
Favazza, A. R., & Rosenthal, R. J. (1993). Diagnostic issues in self-mutilation. Psychiatric Services, 44(2), 134-140.
Fliege, H., Lee, J. R., Grimm, A., & Klapp, B. F. (2009). Risk factors and correlates of deliberate self-harm behavior: A systematic review. Journal of psychosomatic research, 66(6), 477-493.
Goldman-Mellor, S. J., Caspi, A., Harrington, H., Hogan, S., Nada-Raja, S., Poulton, R., & Moffitt, T. E. (2014). Suicide attempt in young people: a signal for long-term health care and social needs. JAMA psychiatry, 71(2), 119-127.
Greydanus, D. E., & Shek, D. (2009). Deliberate self-harm and suicide in adolescents. The Keio journal of medicine, 58(3), 144-151.
Hankin, B. L., & Abela, J. R. (2011). Nonsuicidal self-injury in adolescence: Prospective rates and risk factors in a 2 ½year longitudinal study. Psychiatry Research, 186(1), 65-70.
Hallahan, B., Ryan, T., Hibbeln, J. R., Murray, I. T., Glynn, S., Ramsden, C. E., ... & Davis, J. M. (2016). Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British Journal of Psychiatry, bjp-bp.
Hallahan, B., Ryan, T., Hibbeln, J. R., Murray, I. T., Glynn, S., Ramsden, C. E., ... & Davis, J. M. (2016). Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British Journal of Psychiatry, bjp-bp.
Hawton, K., Bergen, H., Kapur, N., Cooper, J., Steeg, S., Ness, J., & Waters, K. (2012). Repetition of self‐harm and suicide following self‐harm in children and adolescents: findings from the Multicentre Study of Self‐harm in England.Journal of child psychology and psychiatry, 53(12), 1212-1219.
Hawton, K., Rodham, K., Evans, E., & Weatherall, R. (2002). Deliberate self harm in adolescents: self report survey in schools in England. Bmj,325(7374), 1207-1211.
Hawton, K., Zahl, D., & Weatherall, R. (2003). Suicide following deliberate self-harm: long-term follow-up of patients who presented to a general hospital. The British Journal of Psychiatry, 182(6), 537-542.
Hirayama T: Life Style and Mortality. A Large Scale Census-Based Cohort Study in Japan, Vol. 6. New York, Karger, 1990.
Huan, M., Hamazaki, K., Sun, Y., Itomura, M., Liu, H., Kang, W., ... & Hamazaki, T. (2004). Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China. Biological psychiatry, 56(7), 490-496.
Kidger, J., Heron, J., Lewis, G., Evans, J., & Gunnell, D. (2012). Adolescent self-harm and suicidal thoughts in the ALSPAC cohort: a self-report survey in England. BMC psychiatry, 12(1), 1.
Lai, J. S., Hiles, S., Bisquera, A., Hure, A. J., McEvoy, M., & Attia, J. (2014). A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults. The American journal of clinical nutrition, ajcn-069880.
Lewis, M. D., Hibbeln, J. R., Johnson, J. E., Lin, Y. H., Hyun, D. Y., & Loewke, J. D. (2011). Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case-control comparison. The Journal of clinical psychiatry, 72(12), 1-478.
Marriott, B. P., Hibbeln, J. R., Killeen, T. K., Magruder, K. M., Holes-Lewis, K., Tolliver, B. K., ... & BRAVO Group. (2016). Design and methods for the Better Resiliency Among Veterans and non-Veterans with Omega-3's (BRAVO) study: A double blind, placebo-controlled trial of omega-3 fatty acid supplementation among adult individuals at risk of suicide. Contemporary clinical trials, 47, 325-333.
Mischoulon, D., & Freeman, M. P. (2013). Omega-3 fatty acids in psychiatry.Psychiatric Clinics of North America, 36(1), 15-23.
Nanri, A., Mizoue, T., Poudel-Tandukar, K., Noda, M., Kato, M., Kurotani, K., ... & Japan Public Health Center-based Prospective Study Group. (2013). Dietary patterns and suicide in Japanese adults: health centre-based prospective study. The British Journal of Psychiatry, bjp-bp.
Nixon, M. K., Cloutier, P., & Jansson, S. M. (2008). Nonsuicidal self-harm in youth: a population-based survey. Canadian Medical Association Journal,178(3), 306-312.
O’Neil, A., Quirk, S. E., Housden, S., Brennan, S. L., Williams, L. J., Pasco, J. A., ... & Jacka, F. N. (2014). Relationship between diet and mental health in children and adolescents: a systematic review. American journal of public health, 104(10), e31-e42.
Psaltopoulou, T., Sergentanis, T. N., Panagiotakos, D. B., Sergentanis, I. N., Kosti, R., & Scarmeas, N. (2013). Mediterranean diet, stroke, cognitive impairment, and depression: A meta‐analysis. Annals of neurology, 74(4), 580-591.
Rucklidge, J. J., & Kaplan, B. J. (2013). Broad-spectrum micronutrient formulas for the treatment of psychiatric symptoms: a systematic review.Expert Review of Neurotherapeutics, 13(1), 49-73.
Sarris, J., Logan, A. C., Akbaraly, T. N., Amminger, G. P., Balanzá-Martínez, V., Freeman, M. P., ... & Nanri, A. (2015). Nutritional medicine as mainstream in psychiatry. The Lancet Psychiatry, 2(3), 271-274.
Tanskanen, A., Hibbeln, J. R., Hintikka, J., Haatainen, K., Honkalampi, K., & Viinamäki, H. (2001). Fish consumption, depression, and suicidality in a general population. Archives of general psychiatry, 58(5), 512-513.
B2695 - The Intergenerational effects of Educational Attainment - 28/06/2016
In this project we will investigate the intergenerational effects of parents educational attainment on the educational outcomes of their children. We will investigate how much of the observed correlation between parents and children's educational attainment is due to shared genetic variants and what the direct effect of increasing parents educational attainment is on the education of their children.
B2701 - Social and Biological Processes Linking Stress and Suicide Attempts During Development - 15/06/2016
Suicide is a leading preventable cause of death. This project will study the
social, psychological and biological mechanisms linking childhood trauma and adversity to
suicide attempts. Results will inform intervention efforts and predictive models aimed at early
identification.
B2700 - CLOSER - extension to WP 2 Harmonisation of socio-economic status and qualifications - 15/06/2016
This project aims to clean and systematically code existing text data on parental occupation (mother and partner), which were collected at when teh ALSPAC children were aged 10/11. The rational of this exercise is to provide the CLOSER collaboration with harmonised parental social class and occupational data. This will maximise data availability by increasing the pool of available occupational and social class data already harmonised between the CLOSER cohorts, and will permit greater cross-cohort analyses by individuals interested in utilising such data in their research projects. As the only main cohort currently without available occupational and social class data at this key life stage this project seeks to make a major contribution to the availability of key-variable harmonised data within the CLOSER group.
B2696 - Making comprehensive ALSPAC questionnaire metadata available on the Maelstrom-Research website - 15/06/2016
The ALSPAC project is already one of 100 studies in the IALSA Network (Integrative Analysis of Longitudinal Studies of Ageing) and key scientific information about the design and evolution of ALSPAC is therefore made publically available via the website of the Maelstrom Research Group, based at McGill University in Montreal, Canada (www.maelstrom-research.org). This is because IALSA has elected to make basic information about all studies in its network available via Maelstrom Research. A/Prof Isabel Fortier (co-applicant 1 on this application) is Principal Investigator of Maelstrom Research Group and Prof Paul Burton (Principal applicant on this application) is a member of the Maelstrom research group.
As well has lodging basic information about their studies, 44 of the 100 projects in IALSA have also lodged detailed metadata about the variables in their questionnaires on the Maelstrom website. This makes it easier for scientists who may wish to make use of these studies to identify precisely what variables may be obtained from which data collection sweeps. Because the funding flow to Maelstrom has proven to be particularly successful recently, the project is currently able to invest more staff and resources than usual on adding the detailed information representing the complete questionnaire metadata on a number of additional studies. ALSPAC has been given the opportunity to be treated as a priority in this regard, and this proposal represents the formal application to enable this to happen.
B2693 - The causal role of adiposity on disordered eating behaviours - 09/06/2016
This project will investigate whether adiposity (as measured by BMI) is causally related to disordered eating or vice versa.
B2694 - Impact of maternal influences on myopia development - 20/06/2016
The influence of prenatal factors in the determination of conditions such as heart disease, diabetes and obesity is well reported with maternal health and prenatal environment known to influence development throughout the life course. The development of myopia (short sight) has been explored previously with studies concentrating on the growth of the child. Early life and maternal influences on myopia have been examined in two British birth cohorts, ALSPAC and the 1958 Birth cohort, with some association between birth weight and growth being reported. Northstone at al. 2013 (ALSPAC) investigated growth trajectories from birth to age ten years (excluding puberty) and found minimal association between growth over the first ten years of life and the development of myopia, however maternal measures were not included in the analysis nor was growth tracked through puberty, a key time of myopia development. Separate analysis of the 1958 Birth cohort found some evidence of association between mothers’ height and myopia (1% increase in risk per centimetre increase in maternal height).
We are interested in analysing data previously collected by the ALSPAC team detailing measures of vision, degree of myopia and growth (height, weight and obesity) of the participating children through childhood and puberty, and in particular investigate the association of maternal factors such as maternal height, weight and obesity with the development of myopia.
B2692 - The role of DNA methylation in common child allergies - 09/06/2016
This project will investigate the possible role of DNA methylation changes in children as a potential cause of common allergies including peanut, pollen, dust and cat.
B2690 - The impact of Maternal Thyroid Dysfunction during Pregnancy on Behaviour Psychiatric Disorders and other health outcomes among - 09/06/2016
The impact of early life exposures on future neurodevelopmental outcomes has received increasing attention, with the impact of maternal thyroid dysfunction found to be a determinant of offspring cognitive ability. Fetal neurodevelopment is solely dependent on maternal thyroid hormone in the first trimester of pregnancy, and though fetal production of thyroid hormone begins during the second trimester, the developing fetus remains partially reliant on maternally supplied thyroid hormone for the remainder of the pregnancy (1).
Thyroid hormone disorders are major determinants of maternal pregnancy related complications and adverse pregnancy outcomes (2, 3). Maternal hypothyroxinemia has been found to be associated with preterm birth, low birth weight, the head growth of young child, placental abruption, cognitive delay and many other abnormal neurobehavioral development of affected offspring (4-9). Maternal hyperthyroidism is also highly associated with maternal and fetal adverse events, such as pre-eclampsia, miscarriage, stillbirth, preterm birth, intrauterine growth restriction (5). All these adverse events can in turn disrupt the development of the nervous system resulting in offspring poor neurodevelopment.
Exposures during pregnancy may also result in permanent negative health outcomes among exposed offspring and we aim to investigate the impact of maternal thyroid function on offspring’s neurobehavioral and other health outcomes in early childhood and adolescence. Several studies reported that both maternal and neonatal thyroid function status affects the neurophysiology of the offspring prior to adolescence. However, there is a dearth of information regarding its effect on behavioural and psychiatric disorders.
The aim this study is to investigate whether abnormal maternal thyroid hormone levels affect i) the thyroid function of offspring, ii) neurobehavioral development in early childhood and adolescence, iii) offspring’s body size status during delivery, and iv) investigating the effect on late adolescents behavioural and psychiatric disorders.
REFERENCES
1. Escobar GMd, Obregón MaJ, Rey FEd. Maternal thyroid hormones early in pregnancy and fetal brain development. Best Practice & Research Clinical Endocrinology & Metabolism. 2004;18(2):225-48.
2. Stagnaro-Green A, Rovet J. Pregnancy: Maternal thyroid function in pregnancy - a tale of two tails. Nature reviews Endocrinology. 2016;12(1):10-1.
3. Korevaar TI, Muetzel R, Medici M, Chaker L, Jaddoe VW, de Rijke YB, et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. The lancet Diabetes & endocrinology. 2016;4(1):35-43.
4. van Mil NH, Steegers-Theunissen RP, Bongers-Schokking JJ, El Marroun H, Ghassabian A, Hofman A, et al. Maternal hypothyroxinemia during pregnancy and growth of the fetal and infant head. Reproductive sciences (Thousand Oaks, Calif). 2012;19(12):1315-22.
5. Stagnaro-Green A, Pearce E. Thyroid disorders in pregnancy. Nature reviews Endocrinology. 2012;8(11):650-8.
6. Pakkila F, Mannisto T, Hartikainen AL, Ruokonen A, Surcel HM, Bloigu A, et al. Maternal and Child's Thyroid Function and Child's Intellect and Scholastic Performance. Thyroid : official journal of the American Thyroid Association. 2015;25(12):1363-74.
7. Henrichs J, Bongers-Schokking JJ, Schenk JJ, Ghassabian A, Schmidt HG, Visser TJ, et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: The generation R study. Journal of Clinical Endocrinology and Metabolism. 2010;95(9):4227-34.
8. Ganaie MA, Charoo BA, Sofi RA, Ahmed A, Bhat JI. Maternal overt hypothyroidism and neurobehavioral outcome of neonates: A cohort study from an iodine-deficient area of Northern India. Indian Pediatr. 2015;52(10):864-6.
9. Chan S, Kilby MD. Thyroid hormone and central nervous system development. The Journal of endocrinology. 2000;165(1):1-8.