There are multiple evidences in the literature that there is a clustering of energy balance related behaviors in children, however, the link with obesity related outcomes is not always consistent across the studies. Our goal is mobilize several European cohorts, all part of the lifecycle consortium, to achieve greater statistical power, and compare results across European countries.

Stuttering is a complex communication disorder, characterized by dysfluent speech, that can have a profound effect on an individual’s social and mental wellbeing. Up to 11% of children commence stuttering by 4 years of age. Whilst stuttering resolves for many, a third will develop a persistent stutter. Stuttering interventions are effective for some in the preschool years; yet, there are no effective treatments for older children, adolescents or adults, and it is not possible to predict who will develop persistent stuttering. The exact causes of stuttering are still unknown, but genetic factors play an important role.

We hypothesize that common genetic variation makes a substantial contribution to the risk of stuttering and propose that this is most effectively investigated by undertaking a genome-wide association study (GWAS), using a large population-based sample of people who stutter (PWS), recruited via an online questionnaire. Crucially, so far there is no published GWAS for stuttering, a clear gap in our genetic understanding of this disorder.

We are building a global collection of PWS, recruiting adults and children through a concerted media recruitment campaign. Alongside our efforts to recruit PWS directly, we are building a global network of cohorts with information on stuttering via the GenLang Consortium. We intend to combine data from both approaches, in a large-scale GWAS meta-analysis.

Understanding the genetics of stuttering will provide insights into the underlying biology, potentially leading to stratification of stuttering into clinically relevant subtypes, targeted treatment and drug targets. This will lead to better health and socioeconomic outcomes for PWS.

In a current project, we are trying to identify genetic factors associated with pubertal traits in Chilean Children. We are also interested on how genetic ancestry affects these traits. In order to know whether our results on Chileans are unique, we need to replicate the same analyses using a European cohort like ALSPAC.

Asthma is a major non-communicable disease affecting over 12% of children and estimated to affect 339 million people worldwide (1,22). It is a multifaceted and heterogeneous disease with different patterns of incidence and prevalence between children and adults and between males and females (3). Its etiology is thought to be a complex interplay between environmental exposures (such as air pollution, mold, pollen, and the weather), genetic susceptibility, and host factors (such as infections and nutrition); the underlying mechanisms, while not fully understood, may include airway inflammation and control of reactivity and airway tone (4).

Exposure to outdoor air pollutants such as particulate matter (PM) and nitrogen dioxide (NO2) have been associated with both childhood asthma and allergies (5–12). However, whether allergies such as atopic dermatitis (eczema) and allergic rhinitis (hay fever) mediate the relationship has not been well-characterized.

The atopic march, the linear progression starting with eczema with subsequent allergic rhinitis and asthma in later childhood is a well-known concept but it may not capture the trajectories of most children (13–15). Asthma often co-occurs with allergies like eczema and allergic rhinitis but the causal nature of this progression is unknown. Studies suggest that a dysfunctional skin barrier may be a site for allergic sensitization and contributes to the onset of eczema and progression to allergic rhinitis and childhood asthma (16). Eczema has often been found to precede development of asthma, but this is not always the case, with only an estimated 1-in-3 children with eczema developing childhood asthma later on (17,18). Similarly, asthma often co-occurs with allergic rhinitis due to shared common physiology such as heightened reactivity and bronchial hyperresponsiveness (19,20). It is considered a risk factor for asthma, with a 23-year follow-up finding allergic rhinitis three times more likely to develop asthma than those without allergic rhinitis (14,15). However, the evolution of the two appear to be bidirectional; a study in Italy following 99 patients with only allergic rhinitis or allergic asthma over 10 years found that 31.8% of participants with allergic rhinitis developed asthma, while 50% of those with asthma went on to develop allergic rhinitis (21).

In this proposal, we hypothesize that relationships between early-life stressors such as exposure to air pollutants and childhood asthma are at least partly mediated by common allergies and allergic diseases.

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The aim of this study is to explore associations of common adverse pregnancy and perinatal outcomes with offspring plasma/serum-based NMR metabolites and compare associations between those conditions that might result in / reflect fetal undernutrition with those resulting in / reflecting fetal overgrowth. We will also assess whether associations differ by age at NMR measurement in the offspring.

Thyroid dysfunction is one of the most common clinical problems among pregnant women. Before the onset of foetal thyroid function in mid gestation, the foetus is completely dependent on the maternal supply of thyroid hormones, which play a crucial role in the foetal growth and development. The increased requirement of thyroid hormones by approximately 50% during pregnancy is a challenge for the maternal thyroid glands. Our recent systematic review and meta-analysis showed that maternal thyroid dysfunction is associated with neurodevelopmental disorders, such as attention deficit hyperactivity disorder and epilepsy. However, the association between maternal and offspring thyroid dysfunction were only investigated in single studies. The major disadvantage of existing studies included limited sample size and unavailability of confounding variables. This project aims to evaluate the association between maternal and offspring thyroid dysfunction in an individual cohort of larger sample size, with appropriate adjustment for confounding factors. It is expected that the results may provide insights on the clinical practice in handling thyroid dysfunction in pregnant mothers and their offspring.

Partly because of perceived health benefits and environment concerns, vegetarian/vegan diets have become increasingly popular around the globe in recent years. Despite the possibility of low intakes of some nutrients such as protein, omega-3 fatty acids, vitamin D, vitamin B12, iron, calcium, zinc, and choline, evidence suggests that vegetarians have generally better long-term health than their omnivorous counterparts. Pregnancy is a special period in the lifecourse, when foetal development requires increased nutrient intakes and accelerates nutritional depletion, and adequate and balanced nutrition is critical for both maternal and foetal health. Two reviews have suggested that appropriately planned and well-balanced vegetarian/vegan diets during pregnancy may be considered safe for the women and their fetuses. However, little is known about whether these diets will have longer-term effects on offspring health throughout childhood. Vegetarianism is highly socially and culturally patterned, so there is a need to carefully control for confounding to infer causal effects. This PhD aims to study associations between maternal vegetarian diet and offspring health across several domains and to attempt to infer which associations are likely to be causal. It also aims to study the role of DNA methylation and circulating metabolites as mediators of any effects.

It is well established that cardiovascular disease (CVD) begins in childhood. Impairments in vascular function occur before the structural changes of CVD present in the arteries and the progression of CVD is related to CVD risk factors, such as cardiorespiratory fitness, physical activity, body composition and blood markers, in youth. Therefore, there is great interest in understanding how exposure to early lifestyle factors could be related to CVD risk in children and adolescents. Our current project utilising the ALSPAC data (B3455) is investigating the associations between early exposure to cardiorespiratory fitness and body composition with measures of arterial structure and function. However, physical activity and sedentary time are additional important markers of health, and warrant exploration for their potential associations with arterial structure and function at an early age.

Existing paediatric data examining associations between physical activity and/or sedentary time with measures of arterial structure and function are limited by small sample sizes and a subjective assessment of physical activity. Therefore, the current models are unable to account for a suitable number of confounding variables. Also, most studies have used cross-sectional design, and those which are longitudinal have a maximum follow up period of two years. Moreover, independent relationships of physical activity and sedentary time with arterial structure and function, may be altered by an existing interaction between physical activity and/or sedentary time.

Recent experimental data in prepubertal children has shown that the decline in arterial function during prolonged sitting can be prevented by performing 10 minutes of moderate intensity exercise each hour. There is evidence on the interaction between physical activity and/or sedentary time and traditional CVD risk factors, such as body composition and blood markers, in children and adolescents. However, there is a scarcity of data at a population level that examines how sedentary time and physical activity interact in children and how this relates to direct measures of vascular function and structure. Therefore, this project aims to examine the cross-sectional and longitudinal relationships between the early life exposure to physical activity and sedentary time with vascular function and structure from childhood to adulthood, while controlling for traditional CVD risk factors and cardiorespiratory fitness.

Adverse Childhood Experiences (ACEs) are stressful events that occur during childhood and adolescence, and include child maltreatment (i.e. emotional, physical, and sexual abuse and neglect) as well as measures of family dysfunction (e.g. parental divorce/separation, intimate partner violence, substance misuse, mental illness, and imprisonment). People who experience ACEs are less likely to do well in school, more likely to become unemployed, and more likely to have poor health. Furthermore, since people who live in socioeconomic deprivation are more at risk of experiencing ACEs, and also more at risk of poor health, ACEs are one mechanism that could drive socioeconomic inequalities in health. However, most of the research to date has looked at ACEs as a whole, and not asked whether experiencing ACEs at different points during infancy, childhood and adolescence might have different impacts. This is important, because it affects decisions about how we best support people who experience ACEs. If ACEs in infancy have the biggest effect on later outcomes, then focusing support on the early years will be most beneficial. Whereas if ACEs at older ages also cause problems, potentially ‘derailing’ people from their previous educational level for example, that would imply that continued support across the whole of childhood and adolescence is important. At a time when local government budgets are severely stretched, generating evidence to help support the justification and prioritisation of interventions is crucial. At present, our ability to carry out high-quality cost-effectiveness analysis of interventions to mitigate the effects of ACEs is limited by a lack of good evidence on the effects of ACEs on key economic outcomes, and how these effects differ across the life course. In this project, we will plug this gap, using extremely detailed data about experiences of ACEs across the life course, linked with detailed family and socioeconomic data, and repeated measures of educational attainment, employment, and health. We will explore the links between ACEs and education and employment, whether these are affected by the timing, duration and recency of ACE exposure, and the mechanisms underlying the associations.
The 2020 SARS-Cov-2 pandemic is likely to have severe implications for children experiencing ACEs and adults who have experienced ACEs. The ‘lockdown’ measures are likely to lead to increased occurrence of ACEs. Missed schooling is likely to be more detrimental for already vulnerable children, and many children who were entitled to continue attending school during lockdown did not do so. Job losses and reductions in income have been concentrated in the already disadvantaged, and the uncertain job market going forwards will pose a greater risk to young adults without the cushioning of a stable family environment and educational success. Using new data collected during the pandemic, we will assess whether young adults who have experienced ACEs are more vulnerable to the economic consequences of the pandemic, e.g. reduced income, furlough, or job loss. This evidence could provide support to the continued and increased need for the provision of services for people experiencing ACEs at this time.
We will work with key academic and non-academic collaborators to ensure that the results from this project are used to support the case for services designed to support people who have experienced ACEs, including with our results being used directly to improve the quality of cost-effectiveness analyses for interventions.