The inside of the lungs are covered with a thin layer called “surfactant” that is vital for optimal breathing. An infant’s lungs continue to develop throughout childhood and are exposed to a range of allergens and infections. How they respond to these may have a vital role in the development of allergies and asthma, and may be driven by the genetic make-up of the child.

A number of studies already performed support this, but much of the work is on small or selected populations or only looking at one or two genes. Indeed, it may be that a combination of genes is more important, particularly when they influence similar functions. This work aims to identify likely candidate genes, which may impact on lung function and how the lung responds to inflammation and infections, and see how they interact in the population to provide increased risk of infection or allergies.

The main genes of interest in this work are the hydrophobic surfactant proteins B and C (SP-B and SP-C) and the innate immunity proteins surfactant protein D (SP-D) and mannose binding lectin (MBL).

There is substantial evidence from animal and human studies that mother-infant interactions, and the quality of the early life environment, are associated with long-term child outcomes, including mental and physical health and academic achievement. However, what specific aspects of maternal behaviour are important or how to change them through interventions is less clear. Research into the causes and consequences of variations in parenting is important for determining how parenting might be modified to improve long-term health and wellbeing in children.
We propose to include novel measures into the next generation of ALSPAC in order to understand more about how maternal behaviour develops during pregnancy and the impact that it has on the development of the child.
We propose to measure how mothers respond to pictures of baby faces during pregnancy to further understand how women prepare to respond to their babies when they are born. Once the babies are born we propose to use ‘wearable’ cameras in mothers and babies (worn on headbands) to capture naturalistic behaviours. We can then see how mothers reactions in pregnancy relate to how they behaviour after birth. This might help us to understand how to help mothers (who might be struggling, for example depressed mothers) better prepare for motherhood. Finally we plan to measures the child’s ability on a number of important cognitive tasks at age 3 years old, to investigate how different maternal behaviours can promote the development of these skills.

Genetic association studies have identified many genetic variants associated with common diseases such as coronary heart disease. Using the data from these studies it is possible to construct genetic scores which associate with an individuals risk of developing that disease. However, the mechanisms by which genetic variation leads to disease is often not well understood. We are interested in understanding whether natural changes in DNA chemistry (DNA methylation) are involved in the mechanisms of disease. The proposed project will test genetic risk scores to determine whether they associate with patterns in DNA methylation. If such associations exist we can apply causal analysis techniques to determine whether such changes are involved in causing disease or are simply markers of other disease processes.

The strong relationship between childhood adversity and developmental outcomes has generated considerable interest in identifying the mechanisms that explain these associations. A small but rapidly growing body of work has examined the impact of childhood adversity on neural structure and function. However, this work has suffered from lack of attention to identifying the underlying dimensions of environmental experience that might plausibly influence neural development and its behavioral correlates.

We have developed a novel conceptual framework for understanding the impact of adversity on development that differentiates between experiences of deprivation and threat. Deprivation is characterized by low complexity environments are those in which children are not offered an array of cognitive stimulating materials and experience. Threat exposures are those that represent significant threats to survival and activate the neural circuitry underlying fear learning.

This framework is largely based on evidence from small laboratory-based studies of children exposed to different forms of adversity. There are few population-based or longitudinal studies that measure the dimensions of deprivation and threat as well as the cognitive and emotional outcomes that we expect them to predict. ALSPAC is one of the only studies we have found that measures each of these constructs and incorporates a longitudinal design. The current data request is focused on variables that would allow us to test specific hypotheses about how distinct types of environmental adversity in childhood influence cognitive and emotional development.

Social inequalities in health, with people experiencing progressively worse health with increasing deprivation, are present throughout the world. Almost every chronic disease shows this same ‘gradient’ with our social and economic circumstances (the jobs we do, the places we live etc.). Given the wide range of conditions that vary with our social and economic circumstances, it has been proposed that there are some common biological pathways in how these experiences can ‘get under the skin’. This project will look at the relationship between childhood socioeconomic circumstances (based on parental characteristics) and a biological risk score known as allostatic load. Allostatic load comprises a number of biological measures taken from blood samples that aims to measure how our bodies are functioning prior to disease. The aim is to examine how allostatic load varies by socioeconomic circumstances in children aged 9 from the ALSPAC study. Very little evidence exists about the development of allostatic load in childhood and its association with socioeconomic features, although there is good evidence for social patterning in adolescence (greater deprivation being associated with poorer/unhealthier allostatic load scores). This work is particularly important as childhood is a critical period in the development of our bodies and our risk of disease later in life. Understanding when and how our social and economic experiences impact on our bodies is essential if we are to try and improve the health of the population and reduce health inequalities.

Test existing and develop new methodologies for the use of metabolomics data in causality studies for human health

This project will investigate the potential prospective association between overweight/obesity status and hearing impairment and speech/language in a paediatric cohort

We will investigate the relationship between the participants' epigenomes and their educational attainment.

Educational attainment is an important predictor of health outcomes across the life-course, occupational attainment, and cognitive function. Recent studies have identified a number of common genetic variants that are associated with education. The proportion of genetic variance in individual differences in educational attainment is estimated to be around 30%. Furthermore, there is a strong genetic correlation between educational attainment and cognitive function. This highlights the utility in using educational attainment as a proxy measure for cognition in genetic analyses. In addition to examining genetic correlates, which are fixed at conception, one can also study dynamic epigenetic measures such as DNA methylation, which are involved in gene regulation. DNA methylation data can also be used to predict with high accuracy an individual's chronological age (epigenetic clock).

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in the UK and globally. The mechanisms underlying the increased cardiovascular (CV) risk in the young have not been extensively explored in larger, well characterised child study populations. Blood pressure is the strongest risk factor for CVD. Elevated blood pressure in adolescence tracks to adult blood pressure and predicts subsequent cardiovascular risk. It is clear that early life risk factors are main determinants of blood pressure act in early life, but their nature and exact role is unclear, and relations between blood pressure and structural and functional aspects of the circulation have been inconsistent.
Our main aim is to complete and extend the cardiovascular characterisation of the ALSPAC cohort at age 17 as originally outlined in the Early life determinants of blood pressure patterns in young adults (ELBA; funded by Wellcome Trust) study and Growth Related effects in ALSPAC on Cardiac Endpoints (GRACE; funded by British Heart Foundation - ALSPAC Reference: B0300) grants. We will focus on specific hypotheses around cardiovascular structure and function in relation to other relevant measures at 17. We will also assess the importance of early life exposures (e.g. birthweight, trajectories of growth, adiposity and blood pressure) from birth into adolescence and other detailed cardiovascular phenotypic measures on resting and dynamic blood pressure, heart rate, central blood pressure, arterial stiffness and cardiovascular structure and function as assessed by ultrasound and echocardiography at age 17.