Proposal summaries
B3064 - Core Support for TwinsUK Cohort - 06/03/2018
This proposal does not seek access to ALSPAC data, rather it proposes uses a clone copy of some of ALSPAC data processes and infrastructure in order to support the TwinsUK cohort. The processes and infrastructure in question relate to ALSPACs Data Linkage activities and the PEARL Data Safe Haven - the ISO27001 certified policies, procedures, infrastructure for the capture, processing and subsequent analysis of linked 3rd Party routine records with study collected data. Equivalent TwinsUK research and study administration needs would be managed by the PEARL team. ALSPAC and TwinsUK data would remain distinct through this time.
B3065 - Cross-cultural analyses of health-behaviours and metabolite profiles in Adolescence UK vs Malaysia - 03/07/2018
In this study we are going to look at how different lifestyle factors, like foods eaten, timing or frequency of eating, physical activity, sedentary behaviours and their timing or location, combine together to create an overall behavioural pattern score that indicates whether adolescents have good health. We've previously found that a combination of factors is more important for health compared with single factors alone. We also plan to use a new, reproducible laboratory technique, known as metabolomics, to record over 220 measures of blood that indicate a range of metabolic processes. This will help us find out in much more detail than ever before how behaviour leads to better cardiovascular health via metabolic pathways. When we know more about the pathway that leads from lifestyle to disease we will be better able to predict who will stay healthy and who will not from their behaviours. We also plan to explore how excess body weight (BMI) is related to cardiovascular health via metabolic pathways, which could help to find new ways of breaking the link between high BMI and poor health by developing new medications to target specific bits of metabolism that go wrong when body weight increases.
We'll be using information from diet diaries, activity monitors and blood samples that have already been provided by Children of the 90s participants when they were teenagers. We'll be combining this with information from another group of teenagers that live in Malaysia, using an approach called cross-cultural analysis, which will enable us to be more certain that any associations we see between behaviour and metabolism or metabolism and cardiovascular health are really true and not just coincidental.
B3063 - Genetic Determinants of Early Childhood Caries - 15/02/2018
Early childhood caries (ECC) is tooth decay that effecting children 71 months or younger. It is the most common chronic disease of childhood. It is caused by the production of acid by bacteria naturally located in the mouth when the child consumes sugary foodstuffs. Genetic factors have been shown to be important in how likely a child is to develop ECC. this study will investigate whether any common changes in the genetic code are related to the development of this condition. Similar work has been conducted in ALSPAC previously however this project aims to use more detailed measures of tooth decay. This work is part of a larger group of work being conducted by a research group in Pittsburgh USA.
B3062 - Correlation between enzymatic and NMR creatinine measurements in blood - 20/02/2018
With this pilot we want to compare two methodes for measuring creatinine (a marker for kidney function) in blood.
The most widley used method for measuring creatinine in clinical practice is called the "enzymatic method".
In the ALSPAC cohort, "NMR" (Nuclear Magnetic Resonance spectroscopy) has been performed on blood samples withdrawn from the participants, in order to measure a large amount of different markers. These assessments include also creatinine measurements.
We intend to measure blood creatinine with the "enzymatic method" in 100 samples in which "NMR" has already been performed, to see if the results obtained with these two methods are similar.
The results of this pilot will be used for a bigger ALPAC proposal, concerning kidney and vascular function in children and young adults.
B3060 - Cohorts as Platforms for Mental Health research CaPMH - 20/03/2018
B3059 - Genetic liability to cleft lip/palate and DNA methylation in the general population - 07/02/2018
Cleft lip and/or palate (CL/P) is one of the most common birth defects, affecting around 1 in every 700 births.
DNA methylation appears to be associated with non-syndromic cleft lip and/or palate (CL/P), with three possible explanations: 1) DNA methylation causally affects CL/P, 2) CL/P causally affects DNA methylation, or 3) the association is confounded by genetic or environmental factors.
If DNA methylation is associated with genetic risk for CL/P in the general population, this would further suggest there is an association between CL/P and DNA methylation. This finding would have important implications for our understanding of the aetiology of CL/P.
We will assess whether genetic variants associated with CL/P are associated with variation in DNA methylation in the general population using ALSPAC.
B3058 - Neurocognitive effects of prenatal psychotropic medication exposure throughout development - 13/03/2018
The goal of this project is to evaluate how maternal use of antidepressants and/or anxiolytic medication during pregnancy may have long-lasting consequences on a childâs neurocognitive development. The overall use of prescription medication (particularly antidepressants) by pregnant women has increased steadily over the past three decades. These medications are able to pass the placental barrier and are secreted in breast milk, which raises concerns about adverse effects on a childâs neurodevelopment. Additionally, maternal mood directly influences fetal and infant development through biological, genetic and indirect environmental mechanisms. Therefore, the benefits and risks of receiving pharmacological treatment during pregnancy must be assessed on an individual basis. Recent studies have demonstrated an increase risk in neurodevelopmental disorders such as autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) when exposed to antidepressants prenatally. However, very little research has explored possible effects of prenatal exposure on the developmental trajectory of cognitive skills and language/communication abilities. To date, no studies have explored possible interactions between medication exposure and genetic factors in these cases.
B3055 - Assessing the role of martial status on sexual timing and the association between breast development and sports participation - 31/01/2018
Data is required to test hypotheses regarding age of menopause and adolescent sports participation based on breast size:
Hypothesis 1: Women who are single/divorced will experience the menopause at an earlier age than women who are married/in a relationship.
Hypothesis 2: Sexually active women will experience a later menopause than their counterparts who do not have sex/have sex less frequently.
Hypothesis 3: Sports participation during adolescence is contingent upon female breast size/development.
For the first two hypotheses, maternal age of menopause will serve as the dependent variable, with marital status and sexual activity acting separate predictors. Control variables will include: socioeconomic status, whether a smoker or not (and frequency of such), BMI, reason for period stopping, age of first and last birth, amount of children, inter-birth interval, contraceptive use, HRT use, ethnicity, age of respondent, and age of first period. The purpose of this study is to assess the causation associated with marital status/sexual activity and age of menopause. While previous studies have found an association between being single/divorced and an earlier age of menopause, it is unclear whether people are single because they had the menopause earlier, or whether the menopause occurred earlier as a result of their marital status. If the latter is found, we will attempt to use evolutionary theory to explain the phenomenon, with a similar principle being applied to level of sexual activity.
The third hypothesis will investigate whether females with larger breasts participate in sports less frequently. Once again, we will analyse the results from within an evolutionary framework, utilising the mismatch hypothesis. Should women with larger breasts participate in sports less, then it may be that there is a trade-off between reproductive success and physical health; for, while larger breasts are positive for reproductive purposes, they may be hindering in regards to exercise and physical fitness. Here, sports participation serves as the dependent variable, with breast development being used as a predictor. Control variables include ethnicity, BMI, maternal socioeconomic status, gynoid lean and fat mass, smoking status, age at completion, and timing of first period.
All hypotheses will be tested using three separate event history models.
B3057 - Sun exposure and mental health - 31/01/2018
It is widely accepted that climate and season have an effect on psychological traits(1,2). General mood and mood disorders such as depression, anxiety, bipolar disorder and particularly, seasonal affective disorder, have been shown to vary with seasonality, weather, latitude and exposure to sunlight(3â7). For instance, in summer mania admissions and suicidal behaviour were reported to be higher(8,9) and depressive episodes less frequent(8). Whilst direct and indirect sunlight was found to influence the sleep cycle, anxiety and depressed mood(4).Biological explanations for this relationship involve neurotransmitter regulation and vitamin D synthesis. Sunlight exposure on the retina stimulates intrinsically sensitive retinal ganglion cells, and as a consequence the secretion of melatonin, which is critical for regulating the sleep-wake cycle (circadian rhythm). Sunlight also plays a role in the production of serotonin, a neurotransmitter that elevates mood, whereas bright light affects endocrine and neurophysiological responses in the brain that trigger alertness(4). Additionally, sun exposure is the main source of the hormone vitamin D, which exerts its biological effects throughout the body (at least 36 human tissues have been found to contain vitamin D responsive elements, including the brain)(7). Vitamin D deficiency has been associated with mental disorders and increased depressive symptoms in a range of populations, as well as with poorer cognitive performance(5,10). In an earlier study carried out in ALSPAC children we generated polygenic scores, using polymorphisms in pigmentation genes, that were strongly associated with the participantâs pigmentation characteristics and in turn with their reaction to the sun and use of sun protection(11). In this new study we would like to explore the potential association of similar polygenic scores âas proxies for sun exposure- with mental health problems experienced by ALSPAC now young adults and their mothers.
References
1. Kent ST, McClure LA, Crosson WL, Arnett DK, Wadley VG, Sathiakumar N. Effect of sunlight exposure on cognitive function among depressed and non-depressed participants: A REGARDS cross-sectional study. Environ Heal A Glob Access Sci Source. 2009;8.
2. Beute F, de Kort YAW. Salutogenic effects of the environment: Review of health protective effects of nature and daylight. Appl Psychol Heal Well-Being. 2014;6:67â95.
3. OâHare C, OâSullivan V, Flood S, Kenny RA. Seasonal and meteorological associations with depressive symptoms in older adults: A geo-epidemiological study. J Affect Disord. 2016;
4. An M, Colarelli SM, Brien KO, Boyajian ME. Why We Need More Nature at Workâ¯: Effects of Natural Elements and Sunlight on Employee Mental Health and Work Attitudes. PLoS One. 2016;11:1â17.
5. Berk M, Sanders KM, Pasco JA, Jacka FN, Williams LJ, Hayles AL, Dodd S. Vitamin D deficiency may play a role in depression. Med Hypotheses. 2007;69:1316â9.
6. Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, Baethge C, Bauer R, Baune BT, Bellivier F, et al. Influence of light exposure during early life on the age of onset of bipolar disorder. Journal of Psychiatric Research. 2015.
7. Stewart AE, Roecklein KA, Tanner S, Kimlin MG. Possible contributions of skin pigmentation and vitamin D in a polyfactorial model of seasonal affective disorder. Med Hypotheses. Elsevier Ltd; 2014;83:517â25.
8. Dominiak M, Swiecicki L, Rybakowski J. Psychiatric hospitalizations for affective disorders in Warsaw, Poland: Effect of season and intensity of sunlight. Psychiatry Res. 2015;229:287â94.
9. Akkaya-Kalayci T, Vyssoki B, Winkler D, Willeit M, Kapusta ND, Dorffner G, Ãzlü-Erkilic Z. The effect of seasonal changes and climatic factors on suicide attempts of young people. BMC Psychiatry. BMC Psychiatry; 2017;17:1â7.
10. Thomas J, Al-Anouti F. Sun Exposure and Behavioral Activation for Hypovitaminosis D and Depression: A Controlled Pilot Study. Community Ment Health J. Springer US; 2017;0:1â6.
11. Bonilla C, Ness AR, Wills AK, Lawlor DA, Lewis SJ, Davey Smith G. Skin pigmentation, sun exposure and vitamin D levels in children of the Avon Longitudinal Study of Parents and Children. BMC Public Health. 2014;14:597.
B3054 - Religion Cooperative Parenting and Child Outcomes - 31/01/2018
Across the Western world, many people have left or are leaving religions and adopting secular lives. Yet, despite the growing number of secular people in the Westâon the global scaleâreligion is growing. The contemporary resilience of religion is in large part due to the high fertility of many religious people. Indeed, even in Western societies, religious people tend to have more children than their secular counterparts. While many people are turning away from religion, secular communities are not growing as fast as high fertility religious communities.
The high fertility of many religious communities represents a paradox. In modern societies, children born to large families face obstacles to flourishing because parents have limited resources, and each child draws more of those resources. For example, children with a larger number of siblings are smaller in stature, face greater mortality risks, and have lower socio-economic success in adulthood. Yet, despite the higher fertility of religious communities, children born to religious parents appear buffered from the costs of high fertility. Conclusive tests, however, have yet to compare secular and religious children of similar family sizes in developmental trajectories. This study will take advantage of the unique nature of the ALSPAC study to compare religious and secular individuals on fertility, and compare children in their physiological and health trajectories as a result of their family size and parentâs religious involvement. We will also test the hypothesis that aid from co-religionists helps to offset the costs of the large families of religious individuals.
B3048 - Improving the assessment of body fatness overweight and obesity in UK children and adolescents of different ethnic origins - 31/01/2018
High body fatness, overweight and obesity in childhood are a major UK health challenge. However, body mass index (BMI), the most widely used marker of childhood body fatness, based on weight and height, is very inaccurate. This project will identify more accurate markers of body fatness in children, which are based on simple non-invasive measurements and are also associated with early markers of diabetes and cardiovascular risk. Initial identification of novel body fat markers will use a range of approaches, including (i) using measurements of weight and height more accurately; (ii) using other body build measurements (particularly waist circumference and skinfold thickness) and (iii) using bioelectrical impedance measurements. These approaches will be tested in pooled data from four studies with `gold standardâ body composition measures in children of White, Black and South Asian ethnicity. The cross-sectional associations between novel body fat markers identified in this first stage and early markers of cardiovascular disease and type 2 diabetes risks in childhood and adolescence will then be studied in independent data sets including ALSPAC, to see whether the associations are stronger than those for conventional body fatness markers, particularly BMI.
B3052 - A prospective examination of the influence of ultra-processed food consumption on measures of adiposity and CVD - 31/01/2018
This study will assess if the consumption of industrialized, ultra-processed food is related to body weight, to weight gain, and to other measures of cardio-metabolic disease within the ALSPAC cohort of children.
B3050 - Investigating the effect of electronic cigarettes on platelet function and megakaryocyte epigenetics - 31/01/2018
Recent work has uncovered the effects of cigarette smoking on platelet function. We seek to discover whether we see these effects in individuals using electronic cigarettes.
B3049 - The impact of a mothers early life maltreatment on the cardiovascular risk of her children - 31/01/2018
Cardiovascular disease (CVD) is the leading killer of men and women in Victoria (1). It is well established that individuals who experience maltreatment (physical, sexual, psychological abuse and/or neglect (2)) in childhood are at heightened risk of developing CVD and other chronic diseases in their lifetime. Victoria has one of the highest number of reported maltreatment cases in Australia (2), with girls aged 13-15 particularly vulnerable. For maltreated girls who go on to become mothers in adulthood, preliminary data show that their children have negative health outcomes in the form of physical attributes like low birth weight; even after accounting for parental socio-economic factors (3). To date, no human study has specifically investigated whether maltreatment experienced by a mother in her early life influences the cardiovascular health of her children. In fact, there is no longitudinal study in Victoria or Australia with the capacity to answer this novel question. This proof of concept project will therefore draw on data from over 14,000 pregnant women enrolled in the well-established ALSPAC study; a world-leading, birth cohort study conducted in the United Kingdom using a sample that is highly generalizable to the Victorian population. Should this concept be validated, findings could provide a new approach to CVD prevention that benefits current and future generations.
B3056 - Later-life health consequences in women with hypertensive disorders of pregnancy who carry a functional IGF1R gene variant - 19/02/2018
Pregnancy has long been known to have a major impact on the developing breast and the future risk of breast cancer. Many studies have shown that hypertensive disorders of pregnancy (HDP) are associated with lower risk of breast cancer; and one major study has also demonstrated a significant reduction in risk of other types of cancer. Although this lower risk may be modest in the overall population of women who experience HDP, our recent research has shown that this reduction for breast cancer can be as high as 90% in a subgroup with HDP that carry a common variant in a key growth factor receptor gene (IGF1R). This studyâs initial objectives are to reconfirm the above cancer associations, examine if the risk reduction extends to women with milder increases in blood pressure during pregnancy, and to examine whether these reductions are modified by other pregnancy factors such as prematurity, maternal age, or offspring gender.
Interestingly, HDP has also been shown to be associated with increased later life risk of hypertension and heart disease, indicating that experiencing HDP can have both good and bad long-term health outcomes. Therefore, a second objective is to further explore this association and determine if the same IGF1R gene variant that predicts breast cancer risk also predicts future risk of developing cardiovascular disease.
This study could improve the ability to predict future risk of developing the two most significant age-associated health outcomes that women face, thereby leading to more effective personalized screening and novel prevention strategies.
B3053 - Childhood diet and nutrition and respiratory and allergic outcomes a longitudinal study - 31/01/2018
There are clues that childhood diet may influence respiratory health and risk of asthma and allergies, but the evidence to date only comes from 'snap-shot' studies at one point in time. In order to get a clearer picture of whether diet in early childhood influences the development of respiratory and allergic disorders later in childhood we need large studies which have collected data from the same individuals more than once over time. ALSPAC has collected detailed information about the childrenâs diet at age 3, and about asthma and allergies when the children were age 7 and older. This dataset will allow us to discover whether children who developed asthma had a different diet when they were younger, compared to children who did not get asthma. In particular, we will investigate whether children who eat a âhealthierâ diet (higher intake of fruit, vegetables and oily fish, rich in antioxidants and omega-3 fatty acids) are less likely to develop asthma and lower lung function, especially if they have a particular genetic make-up and are exposed to high levels of tobacco smoke and air pollution.
B3044 - The longitudinal relationship between technology and mental health Adolescence to young adulthood - 01/02/2018
Adolescents are the heaviest users of technology. The proliferation of the types of technology have allowed for greater access and use among adolescents. One potential impact of the use of technology is changes in levels of mental health. How technology use affects levels of mental health in adolescences and later in life has not been fully answered by current research. Additionally, use of technology and levels of mental health differ by type of technology, gender and age. This project will explore how use of technology and mental health are related as adolescentsâ transition into adulthood. We will look at gender differences as well as explore whether the type of technology affects mental health differently.
The UK has many high quality datasets of children and adolescents that may be able to address these questions. We will catalogue the use of technology questions employed in these datasets. Using those questions we will group individuals based on their use of technology and levels of mental health change during adolescence. We will then examine how levels of mental health and use of technology in early adulthood are associated with the adolescent groupings. Both technology use and mental health have been associated with educational attainment and entry into the labour market. Therefore we will extend our analysis to explore the relationships between use of technology, levels of mental health and educational attainment/entry into the labour market.
The findings from this project will inform future policy decisions, research and intervention development.
B3045 - Maths achievement over the primary-secondary school transition the role of psychological biological and social factors - 31/01/2018
The primary-secondary school transition is a pivotal moment in most childrenâs lives, often accompanied by feelings of worry, stress and anxiety. One factor that has been previously associated with the transition to secondary school is a loss in academic achievement. Previous research has suggested a number of factors are related to differing levels of educational success, however, it is unknown how these factors may interact when taking the school transition into consideration.
The academic ability this project is focusing on is maths attainment. Theoretical and empirical research has suggested that maths skills can be altered by mental health issues and memory deficits, as well as parent-child interactions and the schooling environment.
To assess which factors are the most important for maths achievement, the project is investigating biological, psychological, social and environmental factors over 3 stages: pre-school transition, during school transition, and post-school transition.
In the pre-school transition stage, early life factors including a healthy pregnancy and birth as well as the childâs psychological attributes and early parent-child interactions will be explored. Following this, during the transition to secondary school, the focus of investigation will be on the schooling environment and teacher characteristics. The childâs psychological wellbeing and peer relationships during this time will also be examined. After the transition, the variables discussed previously will be investigated to examine whether they can predict later maths attainment at age 16.
To investigate this the study will utilise data from over 14,000 mothers and their children followed up extensively since before birth to assess which prenatal, pre-transition, during transition, and post-transition factors are the most important for improving maths abilities at age 16. A wide range of biological, psychological, and social factors will be investigated. The study predicts that prenatal issues will negatively impact early maths abilities, while positive relationships with parents and peers will lessen their effects. It is predicted that positive school experiences and teacher attitudes will also decrease this impact. Furthermore, it is predicted that greater mental health issues and lower cognitive abilities will decrease attainment.
B3046 - Investigating the impact of second-hand smoke exposure on DNA methylation in the ALSPAC parent cohort - 19/01/2018
The 2006 US Surgeon Generalâs report, based on a comprehensive review of the scientific literature, identified a number of health risks from second-hand smoke (SHS) exposure, including elevated risk of cardiovascular disease and lung cancer in those exposed (1). Furthermore, the report concluded that there is no risk-free level of SHS exposure and that a large proportion of the population is exposed to SHS in their homes and workplaces in spite of progress in tobacco control.
Despite this substantial body of research, the impact of SHS on health remains under dispute, with some large-scale studies not supporting a causal relationship between SHS exposure and tobacco-related mortality (2). One reason for this may be due to misclassification (3), for example where studies based on reports of smoking in a partner underestimate risks. Objective biomarkers, such as cotinine and DNA methylation, can increase the measurement precision of the underlying SHS exposure to reduce information bias due to misreporting, and may also serve as better indicators of later life disease (4).
One previous study conducted using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) showed low levels of cotinine in non-smoking women whose partners smoked (5), indicating a limited biological impact of SHS. However, the association between SHS exposure and DNA methylation, another objective measure which has been found to be a more accurate predictor of long term smoke exposure (6), has not been thoroughly evaluated. While associations between DNA methylation and passive smoke exposure have been identified in relation to intra-uterine exposure to maternal smoking (7, 8), there have been few studies investigating passive smoke exposure postnatally, and those that have been conducted have evaluated methylation at a limited number of cytosine-phosphate-guanine (CpG) sites (9, 10).
Within the Accessible Resource for Integrated Epigenomics Studies (ARIES) subset of ALSPAC, SHS has been assessed in terms of both prenatal and postnatal smoke exposure in the ALSPAC offspring (8). However, Prince et al [unpublished] found that evidence for differential methylation related to passive (parental) smoke exposure in the ALSPAC offspring is likely (residually) confounded by prenatal smoking by the ALSPAC mothers. This risk of confounding (and collinearity between the prenatal smoking and SHS measures) could be reduced by examining DNA methylation in relation to SHS exposure in the ALSPAC adults, assessed based on reported partner smoking status and SHS exposure at work and in the home.
B3047 - FUT2 secretor status infections and auto-immune disease role of maternal genotype and breastfeeding - 01/02/2018
About 20% of people have an inactive FUT2 gene and cannot secrete particular antigens in their body fluids or intestinal tract. These ânon-secretorsâ are more resistant to pathogens that use FUT2 antigens to infect cells, but they are more susceptible to some other pathogens. Non-secretors also have a lower diversity of âhealthyâ gut bacteria, and may be at increased risk for autoimmune diseases including type 1 diabetes, psoriasis and inflammatory bowel disease. However, these associations are unclear because most studies rely on self-reported information rather than firm diagnoses or biological test results.
FUT2 antigens are also secreted in breast milk. They are attached to breast milk sugars that are not digested by babies, but provide a specialized food source for the babiesâ gut bacteria. These bacteria influence the babyâs growth, immunity and metabolism throughout life. A motherâs secretor status therefore affects her babyâs gut bacteria, which in turn affects the babyâs development and health, including its susceptibility to infections and autoimmune disease later in childhood.
Thus, both maternal and infant FUT2 secretor status can affect the health of breastfed children. However, few studies examining FUT2 have accounted for breastfeeding or maternal secretor status, so it is unclear how a âmatchâ or âmismatchâ in mother/baby secretor status might impact the babyâs gut bacteria and risk of infections or autoimmune disease. We will address this intriguing issue using available information, genetic data, medical diagnoses and biological test results from the ALSPAC cohort.