As more people live to old age, dementia is on the rise, but there is currently no effective treatment. This comes at enormous personal, societal and economic cost. I and others have previously shown that a decrease in heart function is associated with early cognitive impairment, however the underlying cause is not clear. It is possible that poor heart function may lead to poor blood flow in the brain, which may be the link. Another possible link between the heart and the brain runs in the opposite direction. Instead of heart problems leading to brain problems, it could be that lower cognitive function as a child leads to heart problems later in life. I will investigate the direction of the heart-brain association in 30yr olds from the ALSPAC cohort, that have had data collected since birth, including genetic, cognitive and heart measures. I will collect new detailed data on the heart and the brain during rest and during exercise. The results of this study are important as dementia is a public health priority. The clinical implications of reduced cognition among people with impaired heart function are considerable. By understanding the underlying mechanisms, we can reduce the burden of both of these conditions.

It is well known that September-born children perform better on school tests than August-borns, most likely because they are "older in the year". This project aims to explore the importance of gene-environment interplay within this context. More specifically, it will investigate whether this September-effect, or the effect of being "old in the academic year", varies with an individual's genetic predisposition, as proxied by a polygenic score for cognitive ability, for educational attainment, and for 'non-cognitive' skills. We will examine the effects on cognitive outcomes such as academic achievement, as well as on non-cognitive skills, such as the children's "strength and difficulties".

We plan to use Children of the 90s to understand the following: (i) whether being smoking, overweight or obese, having higher blood pressure or blood glucose (sugar) or lipids (fat) makes you more likely to become infected with the SARS-CoV2 virus and to have more severe symptoms; (ii) whether having the infection makes these cardiovascular risk factors worise; (iii) whether pregnancy complications (hypertensive disorders of pregnancy, gestational diabetes, having a baby who is small or large at birth, delivering a baby early) that are know to relate to a woman's cardiometabolic health are related to risk of COVID-19 in the mother and their offspring; (iv)is there any evidence that the COVID-19 pandemic and its management is influence decisions about delaying plans to get pregnant / have children and what is the infection rate and severity in couples of reproductive age; (v) is there any evidence that pregnancy increases or decreases risk of COVID-19 risk and severity

Atopic Dermatitis (AD, also known as atopic eczema and eczema) is a common disease affecting 20% of children in the UK and other high-income countries. The major genetic risk factor for AD is loss of function mutations in filaggrin, a critical skin barrier protein. There are many theories around the high prevalence of filaggrin mutations in European and Asian populations and of eczema including some proposals that having a leaky skin barrier and an overactive skin immune system might lead to skin immune cells being activated through the skin resulting in protection against pandemics. The COVID-19 pandemic is associated with substantial COVID-related health problems and deaths.

We will use data from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective birth cohort study questionnaires and clinical visits to identify people with evidence of eczema in childhood, and genetic data to identify people with filaggrin null mutations. We are very familiar with these data in ALSPAC and have very recently analysed these data. We will then determine if people in early adulthood (the age of the cohort at the time of pandemic emergence) with evidence of childhood eczema are at reduced risk of reporting symptoms suggestive of COVID-19. The subsequent analysis will involve assessing if those with filaggrin null mutations (with and without eczema) have reduced risk of reporting COVID-19 symptoms. We will stratify by the presence or absence of asthma to see if the risks vary in these subgroups.

The overall aim of this project is to study how family background influences children’s attainment. We are interested in two questions. The first question is, how do ‘nature’ and ‘nurture’ combine to influence children’s attainment? To answer this question, we will test whether parental education-associated genetics are associated with the quality of parenting they provide to their children. We will test associations with parental behaviour from before a child is born (e.g., smoking, alcohol use during pregnancy), through infancy (e.g. breastfeeding), childhood (e.g. warm, sensitive parenting; cognitive stimulation), and adolescence (e.g. parental monitoring). We hypothesise that parents’ education-associated genetics are positively associated with these changing forms of parental investment across time. These analyses are a replication and extension of two previous papers from our lab (Wertz et al., 2018; Wertz et al., in press). In the proposed study, we will extend our previous work by a) analysing parenting across a wider age range of the child; b) replicating prior findings across several datasets (including ALSPAC); and c) incorporating measures of genetics and parenting from both mothers and fathers. The second question is, how do links between family socioeconomic status (SES) and children’s educational attainment change across time? To answer this question, we will test if the influence of family SES on children’s school performance has remained stable in Britain over time. We will test associations between family SES and children’s educational attainment across childhood, and compare estimates across different cohorts -- including ALSPAC -- from different historical periods. We hypothesise that the effect of family SES on children’s education will be relatively stable across time. Overall, this project will advance our understanding of the intergenerational transmission of educational attainment.

Depression has become a common mental illness, and It is crucial to establish and study depressive symptoms through early adolescence across adolescence to early adulthood. It is vital to characterize specific causes and certain types of depression in populations to help identify critical points for intervention and treatment. Studies on Depressogenic thinking (i.e., negative cognitive styles) in early adolescence suggest there is an association with the development of depressive mood in this age group. However, the long-lasting effect of depressogenic thinking is not known, especially in early adulthood or later ages. This project will examine how different profiles of depressogenic thinking are associated with varying types of depression and depressive mood (e.g., irritability, anhedonia, depressive thoughts, fatigue or sleeping) and identify the mechanisms underlying negative thoughts (styles) and later depression. Although CBT and medication are used in treatment for diagnosed cases of depression, this study may potentially develop early intervention strategies that may target early adolescence to improve depressogenic thinking to prevent depression in early adulthood and beyond.

Improving the mental health of children and young people is a national priority in the UK. The rate of self-harm amongst adolescents ranges from 6.9 to 18.8 % in the UK. Schools can provide an environment that encourages positive mental health at an early age and prevents poor mental health in later years. Positive relationships with peers and positive perceptions of school connectedness (that is, adolescents’ sense of belonging and attachment to school) are associated with increases in adolescents’ psychosocial wellbeing and decreases in the number of mental health issues. School absenteeism is also associated with an increased risk of self-harm. Levels of school absenteeism may be reduced if early school experiences are of a positive nature. There is also an association of suicidal and non-suicidal self-harm with adverse experiences at school and even minor events like not enjoying school or class work and the feeling about teachers being unclear with respect to their behaviour. We will investigate if early school experiences are associated with adolescent self-harm in the ALSPAC cohort.

In response to the COVID-19 pandemic, a questionnaire was put together and sent out to ALSPAC participants. A number of free text responses have been collected as part of that questionnaire and that data will be immensely valuable in understanding the circumstances of the participants during the pandemic. We plan to code this data in order to make the data usable in quantitative analyses and explore recurring themes in this additional data.

Transmission distortion refers to deviation from the normal 50:50 transmission of alleles from parents to offspring. Departures from this ratio can arise from a number of processes including ‘meiotic drive’ where one allele is preferentially transmitted during meiosis, differences in the fertility or viability of gametes, differences in the survival of the embryo, and artefacts due to the selection of the study sample. The identification of loci which exhibit transmission distortion is not only of substantial biological interest, but is also desirable for the correct interpretation of genetic linkage and association studies.

NB. To be clear we already have the ALSPAC GWAS data required to perform the analyses listed as part of this project and so do not need to be sent any additional data. We are merely requesting permission to conduct analyses and for new staff to access the data.