The goal of our research proposal is to study the interplay between genetic influences and home and school environments in the context of child development. We aim to understand how maternal and child genes jointly determine parental investments, the role of parent-child interactions and daycare access in mediating genetic influences for skill formation, and epigenetic channels through which the childhood environment can influence children’s cognitive and behavioral development.

The prevalence of childhood obesity is a growing public health concern which is only expected to increase in the forthcoming years1. Previous studies have shown that children who become obese are at much higher risk of disease in later life, such as diabetes, hypertension and coronary heart disease2. Along with lifestyle factors such as physical activity and diet, there is mounting evidence that genetic factors also contribute substantially towards early life adiposity. Research to better understand this genetic component therefore holds considerable potential in terms of preventive strategies.

Despite their prevalence, little is known about the causes of adverse pregnancy outcomes. These include pregnancy loss (miscarriage or stillbirth), hypertensive disorders of pregnancy (HDP), gestational diabetes (GD), poor perinatal mental health, preterm birth (PTB), small for gestational age (SGA) and large for gestational age (LGA). Over 50% of pregnancies are affected by any of these outcomes, however we are unable to accurately predict their occurrence. Consequently, antenatal care currently stratifies women for different intensity of antenatal monitoring based on antenatal history, age and parity. Beyond early delivery (e.g. to prevent pregnancy loss or severe morbidity in mother or child), and stepwise treatment (from lifestyle through oral hypoglycaemic medication to insulin) for GD, there are few effective treatments to prevent these outcomes. Recent evidence showing that glycaemia-related differences in foetal over-growth predate the time in gestation of diagnostic tests highlights the need for better early prediction tools.
By identifying women at a high risk of pregnancy-related disease, we can maximise healthcare facilities, resources and screening strategies to allow for earlier diagnosis of these disorders. More sensitive and accurate predictive and stratification measures can assist with alleviating the burden on mothers and healthcare providers by redistributing maternal care resources. Incorporating genomics, epigenomics and metabolomics approaches will contribute towards a more cogent understanding of reproductive and perinatal health and disease11.

The number of eggs in a woman’s ovaries is determined by a) how many eggs she was born with, and b) how quickly they diminish during her lifespan. Because the total number of eggs she will ever have is established while forming in her mother’s womb, it is important to know if there are any factors in that prenatal environment that may affect the development of the eggs within the ovaries. Women with fewer eggs may suffer later in life from infertility or early menopause. Several studies have shown through experiments with animals that paracetamol taken by the mother while pregnant may have harmful effects on the reproductive function of the resulting female offspring. However, no studies have examined this in humans. In animal models, there are three proposed mechanisms for the effects seen in the female offspring: 1) disruption of the chemical signaling from the brain to the ovaries to induce puberty, resulting in earlier age of the onset of periods (which in human studies may be associated with earlier onset of menopause), 2) disruption of the natural menstrual cycle, resulting in shorter menstrual periods (which in human studies may be associated with earlier onset of menopause), and 3) formation of fewer follicles (eggs) in the ovaries, which can be approximated by measurement of anti-mullerian hormone (AMH) in the blood. Given that paracetamol is used worldwide as the analgesic of choice during pregnancy it is of critical importance that large-scale studies of humans be performed to investigate this association. This study will look at children of mothers who did and did not use paracetamol during their pregnancies and compare 1) the age of their first period, 2) how regular their periods are, and 3) their AMH levels.

Cigarette smoking causes an estimated 120,000 deaths per year in the UK and costs the NHS about £2.6bn per year. Quitting smoking is therefore desirable but can be difficult even with professional support. A recent strategy for quitting is the use of e-cigarettes because they can be used to vary nicotine intake, their vapor does not contain known cancer-causing agents found in cigarette smoke, and their use closely mimics cigarette smoking behavior. However, these attractive features can lead to long-term use, and little is known about the resulting health outcomes because e-cigarettes have only recently become widely used. We plan to investigate these potential health outcomes by measuring the effects of e-cigarette use on DNA methylation in saliva and in blood. These effects will then be linked to health outcomes using Mendelian Randomization and publicly available genetic associations.

Adverse childhood experiences (ACEs) are major risk factors for psychopathology. For example, children exposed to abuse, neglect, and dysfunctional home environments have an elevated risk of several later psychiatric conditions. However, as highlighted by a new report by the UK Science and Technology Select Committee (November 2018), it is unclear whether ACEs cause psychopathology, or whether the associations reflect confounding by genetic and environmental factors. For instance, children exposed to some ACEs (e.g., family psychopathology or substance abuse) might inherit genetic risk of psychopathology from their parents. ACEs also often co-occur with other environmental risks for psychopathology, such as prenatal exposures (e.g., smoking, alcoholism, stress) and postnatal exposures (e.g., poverty). This study will use genetically-informative methods and statistical innovation to disentangle the effects of ACEs from these confounds, and in turn strengthen understanding about the potential causal effects of ACEs in psychopathology.

Maternal mental health is associated with variations in parenting and child wellbeing, however the mechanisms through which it affects child development are still poorly understood. Moreover, personality disorders and dysfunctional personality traits have received even less attention than other clinical disorders such as depression and anxiety, in the context of motherhood.
Thus, this project aims to fill this gap and investigate the effect of maternal dysfunctional personality traits on parenting behaviour and child outcomes.
In fact, personality disorders and dysfunctional personality traits are considered great risk factors for the well-being of the individual and for the potential negative effect on the child development. However, there is still no strong evidence about the extent and the causal pathways of how dysfunctional maternal features are affecting offspring wellbeing.
The aim of this project is to investigate the intergenerational effect of maternal mental health on the offspring using multi-generational ALSPAC data we will have the opportunity to explore the associations between different individual and social characteristics, such as geographical data, cognitive, socio-emotional, psychiatric data in mothers, partners and offspring.
Identifying components and potential causal pathways from maternal mental health to emotional infant problems is relevant to the creation of new policies of