DNA methylation (DNAm) plays a central role in gene regulation. It helps to define how cells respond to environmental signals
and, ultimately, contributes to health or susceptibility to disease. DNAm variation is influenced by genetic, molecular and environmental and other factors. However, the amount and the effects of differences in DNAm from one person to another is
poorly understood.
A powerful avenue into researching the functional consequences of changes in DNAm levels is to correlate DNA sequence variants such as single nucleotide polymorphism (SNPs) to DNAm levels to find both local and distal (for example on
other chromosomes) effects. Having completed the largest genetic study of DNAm worldwide to date (through the Genetics of DNA Methylation Consortium) by scanning 10 million SNPs genomewide, we have identified 270k SNP-DNAm associations. This was achieved by analysing about 400,000 DNAm sites in blood, which is only 2% of 28 million DNAm sites across the genome. There is a huge potential for improved understanding of DNAm variation between individuals and its influence on health and disease by studying other regulatory regions of the genome using EPIC arrays, by using cell type interactions and other gene-environmental interactions and by using different types of statistical tests

Adolescents are more likely to become dissatisfied with their body as they could be more easily influenced by their peers and media and internalize bodily norms. In order to alter their body, adolescents may use several strategies such as restrained eating or dieting. Eating restraint and dieting during adolescence could interfere with physical growth and cognitive development, predispose them to weight gain, prompt disinhibited eating, and increase risk of severe eating disorders. Furthermore, health-related habits such as dieting and eating behaviors tend to persist into adulthood.
There is a gap in research about the associations between a combination of different dimensions of eating behaviors in adolescence and health behaviors in adulthood. This research aims to address this gap by studying how adolescents with distinct profile of eating behavior dimensions, including restrained eating and uncontrolled eating, differ from each other during their adulthood in terms of body composition and food preferences. Findings could assist in identifying adolescents at higher risk of obesity and less healthy food choices with regards to dimensions of eating behavior.

Trauma is a transdiagnostic risk factor for posttraumatic stress disorder (PTSD), major depressive disorder (MDD), increased alcohol use, and alcohol use disorder. Additionally, these conditions tend to co-occur, and are genetically-influenced. Decades of work has emphasized the importance of count, type, and timing of traumatic events on these mental health outcomes. However, most work has not examined these mental health conditions simultaneously and very few have investigated their effects over the course of development. This proposed study will examine the role of trauma characteristics on these outcomes across childhood into adulthood, via the use of multiple longitudinal datasets--ALSPAC, as well as two others (Add Health, a nationally representative sample, and ABCD, a diverse sample of children aged 9-10 across the US). This study will also use cutting edge genetic methods (genomic structural equation modeling-derived polygenic risk scores/PRSs) to examine the genetic influences on these conditions, as well as investigate potential interactions between genetic risk and trauma characteristics.

Becoming a parent is an important life event that has a significant impact on the way that we live our lives.
This project will look at how having a child impacts new parents’ mental health and well-being, by using information about ALSPAC participants before they have had children, and seeing how this changes afterwards.
This will help us to understand which parts of our well-being are affected by having children, when this happens, and why different people react differently to becoming parents.
By understanding the experiences of new parents better, we can work towards interventions that support parents’ well-being at this important time of their lives.

Gambling disorder (persistent/recurrent gambling) can be harmful to health/social wellbeing. Previous research suggests that stressful life events, such as child maltreatment increase likelihood of gambling disorder. However, these studies rely on young adults remembering if stressful life events that happened long ago, rather than asking about these events close to when they happened. We also do not know much about the influence of other types of Adverse Childhood Experiences (e.g. parental mental health problems). We plan to look at the influence of a range of Adverse Childhood Experiences on gambling disorder, using data that have followed individuals up regularly since birth until their 30's.

Child maltreatment and childhood neurodevelopmental disorders (Autism and ADHD) are both associated with increased risk of cardiovascular disease and premature mortality in adulthood. Child maltreatment and neurodevelopmental disorders commonly co-occur. Previous work has explored the associations of these exposures individually with adult outcomes but not explored them together. This study aims to explore the association of neurodevelopment and maltreatment with cardiovascular risk factors in young adults, in particular looking for any interaction between the two exposures.

Multimorbidity is the presence of multiple long-term health conditions. People with multimorbidity tend to have worse quality of life, and to be high users of the health service. Mental-physical multimorbidity (MPMM) is a specific form of multimorbidity, typically defined as the presence of at least one mental health condition and at least one physical health condition. People who experience MPMM have more complex health needs than people with only physical health problems or only mental health problems. Each set of health problems may make the challenges of the other set worse, leading to worse quality of life for these patients. Poverty and other measures of deprivation are strongly linked to MPMM, making it a key driver of health inequality.

Research on MPMM is limited, but most studies that do exist focus on adults. However, data from primary care records suggest that 2.5% of 10-19 year olds and 11.1% of 20-29 year olds have MPMM. The true level of MPMM in children and young people will be much higher than this, as many health conditions, particularly mental health conditions, are poorly recorded in health records. Children and young people who already have MPMM are likely to go on to experience complex health needs across their life course, and represent a challenging group for the health service. Understanding who comprises this group, and the determinants and consequences (both for the health service and for the young people themselves) is crucial to identify potential intervention points to reduce the incidence of MPMM and to mitigate its adverse consequences.

In this project, we use birth-cohort data from three studies in the UK and Brazil to explore how and when MPMM occurs in children and young people, estimating the prevalence of overall MPMM and of specific combinations of health conditions. We will also examine the causal determinants of MPMM, and the consequences for young people (including education, employment, pain, health-risk behaviours, and wellbeing) and the health service. Studying both causes and consequences will allow us to reach conclusions about potential intervention targets both for preventing MPMM and for mitigating its adverse effects, and to quantify the potential gains from interventions to prevent MPMM or supporting young people with MPMM. Using data from both a high income country and a middle income country allows us to explore setting-specific patterns, causes, and consequences of MPMM – essential for understanding how tailored interventions must be to the local setting. Using birth cohort data allows us to circumvent the problems of under ascertainment of health conditions in administrative health records; linked health data in the UK cohorts will allow us to quantify this problem.

Studies have suggested that waist (cm)/height (cm) ratio (WC/H) is a useful alternative measure of central adiposity and obesity related metabolic risk in adults and children than body mass index (BMI) (1-3). In practice, BMI has shown poor performance in certain cohorts and does not indicate an individual’s distribution of fat. WC/H focuses on central adiposity, a known cardiometabolic risk factor for adults and children. Furthermore, calculating BMI requires weighing equipment, a calculator and potentially software/charts. WC/H only needs a tape measure, uses a simple calculation and has a pre-defined ratio to define risk across participant types (cited as >0.5).

NICE have recently recommended the use of WC/H alongside BMI to assess and predict weight-related conditions. There is currently a paucity of research describing the life course patterns of WC/H or demonstrating that it provides equal or improved prediction in metabolic health from childhood to adult life compared to BMI. There is also little evidence relating WC/H to outcomes or intermediates related to central adiposity in particular – e.g., hypertension and non-alcoholic fatty liver disease.

This study aims to 1) chart the trajectory of WC/H compared to BMI through ages 7, 11, 15 and 24, 2) examine associations of WC/H or BMI, and blood pressure and liver health at these ages and 3) compare these associations to explore if WC/H is more discriminatory in defining risk. This will provide additional evidence for the recommendation of an easier measure to assess clinical need for weight management interventions across childhood and adolescence.

References
1. Ashwell M, Gibson S. Waist-to-height ratio as an indicator of 'early health risk': simpler and more predictive than using a 'matrix' based on BMI and waist circumference. BMJ Open. 2016 Mar 14;6(3):e010159.
2. Savva SC, Tornaritis M, Savva ME, Kourides Y, Panagi A, Silikiotou N, Georgiou C, Kafatos A. Waist circumference and waist-to-height ratio are better predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes Relat Metab Disord. 2000 Nov;24(11):1453-8.
3. Khoury M, Manlhiot C, McCrindle BW. Role of the waist/height ratio in the cardiometabolic risk assessment of children classified by body mass index. J Am Coll Cardiol. 2013 Aug 20;62(8):742-51.

Previous research has shown association between exposure to long-term air pollution and adverse lipid profiles. Fewer studies have been performed using metabolomics, which identify and quantify small molecules to represent an organism’s metabolic state. A metabolic signature in the blood associated with ambient air pollution exposure is plausible given some ambient air pollutants (ultrafine particles and gaseous air pollution) have been reported to enter the bloodstream directly from the lungs. Most research in this area has focused on adulthood, and little evidence is available in younger ages. This study aims to assess the metabolomic signature of air pollution in childhood.