Proposal summaries
B3276 - Does the way overweight/obese mothers feed their children contribute to the development of childhood obesity - 21/03/2019
Child overweight and obesity is a serious increasing health problem in the UK. Overweight/obesity often continues in adulthood and increases the risk for developing many chronic disease. Having a mother that is overweight or obese means it is more likely that the child will be overweight or obese also, perhaps through the establishment of unhealthy eating patterns and food preference in early childhood. The role of the mother in feeding her young child is likely to be critical in this process.
B3277 - Impact of leanness on type 2 diabetes liability - 21/03/2019
We know that obesity (high body fatness) is a major risk factor for type 2 diabetes. We also know that obesity is very difficult to reverse, and that we need to find ways of preventing type 2 diabetes when fat loss is not feasible. Muscle tissue â the other major body compartment â is likely beneficial for health, but little is known about which aspects of muscle (e.g. whether volume or strength) matter most for the earliest stages of type 2 diabetes, and how these benefits compare with the harms of fat. This project aims to use repeated measures data from ALSPAC offspring and parents to determine which aspects of muscle â whether higher volume based on body scanning, higher strength based on hand grip tests, or higher quality based on a combination of strength and volume â has stronger effects on an extensive set of detailed metabolic traits related to type 2 diabetes susceptibility. It also aims to determine how benefits of muscle compare with harms of fat, and whether muscle interacts with fat in relation to early stages of disease. Altogether, these results should help us to better understand which aspects of body composition are most important to target with limited public resources in order to prevent type 2 diabetes, and whether boosting muscle would help prevent type 2 diabetes when fat loss is not feasible.
B3275 - Cognitive skills and the development of strategic sophistication - 04/04/2019
Theory of mind (ToM) is associated with childrenâs early social relationships, communication skills, self-judgement, self-control and loneliness in young adulthood. ToM also correlates with childrenâs sophistication in strategic environments, where they need to predict othersâ behaviour and best respond to those predictions. Therefore, ToM appears to interact with important determinants of decision-making. There are, however, striking differences in ToM among children of a given age. This project tries to understand this variation in ToM. Specifically, we are interested in studying how school characteristics, parental characteristics (such as income), and personal characteristics (such as personality and cognitive skills) affect the development of ToM. The project will further study how the level of ToM in early life and the variation of ToM over time associate with educational achievement, educational choices and labour market outcomes in young adulthood.
B3271 - Can early childhood experience predict physical activity behavior and cardiovascular health two decades later - 12/03/2019
The goal of this project is to study whether babies' experience during the first three years such as parenting, activities, and home and neighborhood environment can affect longer-term health behaviors and cardiovascular health two decades later.
B3247 - Different effects for different people investigating the impact of the neighbourhoods on educational attainment - 12/03/2019
Understanding how places impact peopleâs health, education and employment has long been a focus of policy and academic discourse. The idea that the area someone grows up in can have an impact on their later life is appealingly intuitive. However, accurately determining the effect that place has on peopleâs lives is difficult, and previous research has shown a wide range of supposed effects ranging from harmful to beneficial to none. For example, people who live in extremely deprived neighbourhoods have poorer chances of gaining employment, are more likely to participate in deviant behaviour, and are more likely to be unhealthy in later life. However, other academic research has suggested that the presence of positive effects is the result of unmeasured confounding factors including selective residential mobility, alongside individual characteristics such as family environment and genetic composition.
Whilst longitudinal analysis has long been embraced by the neighbourhood effects literature it has tended to focus on the adults. As a result, the context in which children grow up has been relatively overlooked and although environments experienced in adulthood are important, experiences during childhood condition adult outcomes strongly. The research proposed in this proposal is designed to investigate the way in which neighbourhoods effect children as they transition from childhood into adulthood once factors relating to family and school context, personality, and genetics have been considered. It will use cutting edge methods to provide new insight into the way in which effects at multiple scales combine and interact to influence importance social outcomes. In particular, the work will bring together the ideas of what, who and where someone is as a means to understand their development.
B3272 - Infertility and Cardiometabolic Health - 12/03/2019
This project aims to establish if and how infertility affects the risk of cardiovascular disease in both men and women. By using genetic markers as instrumental variables, we will establish any causal relationship between cardiovascular risk factors (smoking, body-mass index, blood pressure, lipids, glucose and insulin) and infertility in both sexes. If we observe a clear link between classical cardiovascular risk factors and infertility, this highlights a role of a pre-existing underlying risk of cardiovascular disease in infertility. We will also examine whether children of infertile couples have a poorer cardiometabolic health compared to children of fertile couples, to understand whether cardiometabolic factors might contribute to the familiar aggregation of infertility. To better answer this question, we will also identify any genetic markers which affect infertility in men and women, to use these as instrumental variables in causal inference methods.
B3274 - Replication of the novel gene PDE11A related to a nose phenotype in the ALSPAC cohort - 12/03/2019
This study is designed to replicate the discovery of the PDE11A gene associated with nose shape derived from 3D radiographs. The replication will be underaken on facial measures derived from ALSPAC 3D surface facial scans.
B3273 - Two-sample Mendelian randomization of Sex Specific Patterns of Autosomal Methylation MR-SSPAM and later life health outcomes - 12/03/2019
Differences in DNA methylation between sexes on the autosomes have previously been found and hypothesised to be contribute to the sexual discordance observed in various traits and diseases. Specifically, an analysis in the ALSPAC cohort determined that over 8,500 sites are differentially methylated between sexes at birth, with the differences persisting in to childhood and late adolescence. Whether these observed differences in DNA methylation between sexes are causal to diseases for which differences in prevalence by sex is also observed is currently unknown. We propose to use Mendelian randomization (a causal inference method) to determine if these differences in DNA methylation are potentially causal to a panel of diseases (and traits) which are known to demonstrate differences in prevalence between sexes observationally.
B3270 - Identification of Genetic Risk Factors for Postpartum Depression - 11/03/2019
B3269 - SOCIOMENT Socioeconomic inequalities in childrens mental health disentangling social causation and selection - 07/03/2019
Children of parents who have limited education, occupational status and/or income are more likely to develop mental health problems than their more advantaged counterparts. However, we do not know whether it is parental socioeconomic position (SEP) which causes children to develop mental health problems, or whereas some other factors, such as parental personality, cause both parental SEP and children's mental health. The aim of this project is to provide new knowledge on the impact of parental SEP and other parental characteristics on childrenâs mental health and the extent to which psychosocial pathways influence development of childrenâs mental health, depending on parental SEP. We will analyze the data using a statistical method of dynamic panel modelling, which substantially enhances the prospect that the observed associations are causal.
We will take the advantage of our on-going longitudinal study, the Trondheim Early Secure Study, of 997 children from a community sample (age 4-16) and will compare the results across countries, employing also the ALSPAC data.
B3268 - To determine early-life environments that have an enduring impact on leukocyte telomere length - 02/04/2019
Telomeres are protective caps (stretches of DNA) at the end of chromosomes. As we age, cells will divide for growth and repair, and telomeres will progressively become worn away, becoming shorter and shorter in length. Eventually when telomeres become really short, a cell loses the ability to divide, which we call "cell senescence". Increased rates of cell senescence means our bodies can less readily repair themselves when damaged because they can no longer make new, healthy cells.The rates at which telomeres shorten are affected by both genetic factors and environmental factors. Premature shortening of telomeres relative to oneâs age is associated with all-cause mortality, as well as risk for age-related diseases and associated risk factors, including: cardiovascular disease, coronary artery disease, type-2 diabetes, major depression, chronic low-grade inflammation (âinflamm-agingâ), chronic obstructive pulmonary disease, and Alzheimerâs disease, amongst others.
Childhood represents a period of accelerated cell division, and consequently telomeres can shorten up to four times faster in children compared to adults. There is compelling evidence to suggest that environmental traumas during this critical period of early life result in persistently shortened telomeres and may even influence the trajectory of telomere shortening through to adulthood. Consequently, designing optimal environments for children (e.g. low stress, optimal diets, exercise regimes, living environments etc.) may halter premature ageing and reduce risk for disease in later life.
This project attempts to better understand which early environments protect from telomere shortening and promote healthy ageing across the life course.
B3266 - Physical activity and eating in the transition from childhood to adolescence - 05/03/2019
Limited physical activity (PA), sedentariness and unhealthy eating increase the risk of non-communicable diseases and conditions that are leading causes of mortality, disability pensioning, extended use of social benefits, years lived with disability, and reduced quality of life. Physical inactivity and unhealthy eating habits thus represent important preventable causes of life years lost1 and years living with disability, implying unnecessary high costs to society. The overarching aim of the project is to ascertain causes of PA, inactivity and unhealthy eating behavior in the transition from childhood to adolescence, a critical phase for passing on healthy PA- and eating habits from early to later ages and thus a crucial periode for promotion of good health and quality of life. We will take the advantage of our on-going, prospective study (The Trondheim Early Secure Study - TESS, n=997) of a representative community sample of children, who have been intensively and repeatedly studied from age 4 to 14, aiming to re-study these participants when 16 and 18 years of age. The ALSPAC data will be used to compare and replicate findings.
B3267 - Offspring adaptation to social isolation Testing a novel prenatal social environment adaptation hypothesis - 05/03/2019
B3265 - Development of a widely applicable tool for phenome scans and data processing - 26/03/2019
While studies examining the effect of an exposure of interest on specific health issues provides important understanding into the determinants of health and disease, it would be arguably more useful to determine, in a single study, the extent that the exposure affects a very large number of health-related traits and diseases. Phenome scans are a particular type of 'hypothesis-free' study, that test the association of a trait of interest with a comprehensive array of phenotypes â the âphenomeâ. They can be used with an approach called Mendelian randomization to search for the causal effects of a trait of interest with potentially many outcomes. Performing a phenome scan is typically non-trivial as the set of phenotypes available in a cohort tends to be highly heterogeneous. Recently, we developed a tool called PHESANT, that allows researchers to conduct phenome scans in UK Biobank. However, currently it is not easy to perform phenome scans in ALSPAC. In this project we will develop innovative software that enables researchers to easily perform their own comprehensive phenome scans in ALSPAC, searching across 'all' phenotypes is this cohort. We will demonstrate this software by searching for the causal effects of education, as an exemplar.
B3263 - Shared genetic pathways influencing normal/abnormal facial shape medical conditions - an international collaboration - 09/04/2019
Historically, craniofacial genetic research has understandably focused on identifying the causes of craniofacial anomalies and it has only been within the last 10 years, that there has been a drive to detail the biological basis of normal-range facial variation. This initiative has been facilitated by the availability of low-cost hi-resolution three-dimensional systems which have the ability to capture the facial details of thousands of individuals quickly and accurately. Simultaneous advances in genotyping technology have enabled the exploration of genetic influences on facial phenotypes, both in the present day and across human history. There are several important reasons for exploring the genetics of normal-range variation in facial morphology.
- Disentangling the environmental factors and relative parental biological contributions to heritable traits can help to answer the age-old question âwhy we look the way that we do?â
- Understanding the aetiology of craniofacial anomalies; e.g., unaffected family members of individuals with non-syndromic cleft lip/palate (nsCL/P) have been shown to differ in terms of normal-range facial variation to the general population suggesting an etiological link between facial morphology and nsCL/P.
- Many factors such as ancestry, sex, eye/hair colour as well as distinctive facial features (such as, shape of the chin, cheeks, eyes, forehead, lips, and nose) can be identified or estimated using an individualâs genetic data, with potential applications in healthcare and forensics.
- Improved understanding of historical selection and adaptation relating to facial phenotypes, for example, skin pigmentation and geographical latitude.
- Highlighting what is known about shared facial traits, medical conditions and genes.
This project will be an advancement on a previous studies undertaken at 15 years of age which has yielded a series of landmark articles. The 15 year old cohort will be recalled at 30 and 3D facial images will be collected for as many of the original 4747 15 year old faces as well as their mothers/fathers and their own offspring.
The computer generated 3D facial images/shells will be important in exploring:
- the link between normal variation and craniofacial anomalies
- heritability of facial features (e.g. overall face size/shape and local features nose, lips chin etc)
- Environmental and shared genetic influences on facial shape and reported medical conditions
- Facial ageing from 15 to 30 years of age
- Forensic science relating to identification of facial types from genetic data
- Engagement of the ALSPAC family in deriving relatedness in parents and offspring
- Enable the research team to lead and collaborate with other international cohort studies/cleft lip and palate/craniofacial anomalies/normal facial variation and shared genetic consortia.
There has been significant progress in the first 6 years of GWAS and facial genetics. With increased sample sizes, improved understanding of shared genetic influences on human traits and advancement in techniques there is likely to be significant further progress in the next 6 years. Understanding the face will explain âwhy we look the way we doâ a range of normality and abnormality that
will be useful in a large number of healthcare applications and forensic science.
B3264 - The continuation of interpersonal violence Investigation into the relationship between bullying and intimate partner violence - 26/02/2019
It is well documented within academic and public policy literature that exposure to violence in all its forms has a detrimental impact on the well-being of all those involved, and is thus a serious public health issue. In particular, attention has been directed towards bullying and intimate partner violence (IPV) as these are two of the most common forms of violence perpetrated and experienced. Individuals who are involved in bullying or IPV as either perpetrators or victims are at an increased risk of experiencing mental health problems (i.e. depression, anxiety, substance use) and greater difficulties in life (i.e. academic decline, financial difficulties, poor physical health). To date the majority of research has investigated bullying and IPV independently of one another in the same individual. The small number of studies which have not, have found that bullying perpetrators are more likely to be perpetrators of IPV and victims of bullying are more likely to be victims of IPV. However these studies have predominantly been conducted in America, have focused on teen dating violence as a form of IPV and have investigated the relationship concurrently. Furthermore very few studies have investigated the continuation of exposure to violence from bullying to IPV by exploring underlying mechanisms which may explain why this is happening for some and not all. As bullying and IPV are interpersonal in nature, factors which influence social interactions and the processing of the social environment and cues may help us to understand the relationship between the two. For example these include the ability to correctly identify emotions and the causes of events and interactions. Identifying individuals who experience both forms of violence and thus experience violence across their lifespan could prove to be an important way to predict and improve the impact on their well-being.
B3262 - The association between pregnancy and change in cardiovascular health - 22/02/2019
It is currently unknown if and what effect pregnancy has on cardiac structure and function.
B3258 - STOP Science and Technology in childhood Obesity Policy - 20/02/2019
B3259 - The EWAS Catalog a database of epigenome-wide association studies - 19/02/2019
DNA methylation is the process of adding a methyl group to a DNA molecule, often changing how the molecule interacts with other cellular factors. Methylation mainly occurs at cytosines in humans, often in the context of a cytosine followed by a guanine (CpG). Epigenome-wide association studies (EWAS) seek to understand the link between DNA methylation patterns at thousands or millions of CpG sites across the genome to various traits and exposures. In recent years, the increase in availability of DNA methylation measures in population-based cohorts and case-control studies has resulted in a dramatic increase in the number of EWAS being performed and published. To make this rich source of molecular data more accessible, we have manually curated a database of CpG-trait associations (with p<1x10-4) from published EWAS, each assaying over 100,000 CpGs in at least 100 individuals. The database currently contains over 500,000 CpG associations for more than 150 EWAS. It is accompanied by a web-based tool and R package that allow these associations to be easily queried. In the near future, we hope this database will be extended to include genome-wide EWAS summary statistics, including over 200 million associations from over 500 EWAS of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N~900). This database will give researchers the opportunity to quickly and easily query EWAS associations to gain insight into the molecular underpinnings of disease as well as the impact of traits and exposures on the DNA methylome. The EWAS Catalog is available at: http://www.ewascatalog.org.
B3261 - Genetic and epigenetic approaches to identify factors influencing paternal participation in birth cohort studies - 19/02/2019
Paternal participation in cohort studies is lower than maternal
The mother is often considered the âgatekeeperâ to paternal involvement
This can introduce selection bias that can make maternal effects appear relatively stronger than paternal effects
For example, a previous study found that paternal participation was lower for mothers from low SEP, ethnic minorities, and those who smoke. This would contribute to any paternal effect of these factors on offspring health appearing smaller and weaker than any maternal effect.
A better understanding of the factors that influence paternal participation will enable researchers to develop strategies to increase paternal participation, thereby reducing these issues with bias. It will also highlight scenarios that might be subject to selection bias, which will help with interpretation of results.
Hypothesis-free approaches, such as those involving genetic and epigenetic âomic data, can help identify factors that influence paternal participation without reliance on/bias from the researchersâ assumptions.
This project aims to use genetic and epigenetic approaches to identify factors associated with paternal participation in birth cohort studies.