Body dysmorphic disorder (BDD) is characterised by excessive preoccupation with perceived flaws in physical appearance (most commonly facial features), which appear minimal or completely unobservable to others. Sufferers typically engage in a range of compulsive and repetitive behaviours, such as extreme grooming rituals, often in an attempt to conceal or correct their perceived appearance flaws. The disorder usually starts during adolescence, with an average onset at age 16. BDD affects about 2% of the general population at any one point in time, although up to 15% experience subthreshold symptoms that are impairing in their own right. The disorder has a devasting impact on quality of life, and is linked with high risk of suicidality. Is it estimated that one in four people with BDD attempt suicide, making it one of the most high-risk of all psychiatry disorders. Despite the prevalence and morbidity of BDD, it remains strikingly under-researched.

There is currently a lack of clarity about how BDD relates to other mental health disorders. BDD was previously classed as a “somatoform disorder”, but was recently reclassified under “obsessive-compulsive and related disorders” in the major diagnostic systems (DSM-5 and ICD-11). This classification remains a focus of debate. For example, data from recent cross-sectional studies have indicated BDD has stronger links with eating disorders and depression than obsessive-compulsive disorder. However, the longitudinal associations of other psychiatric disorders with BDD remain unclear. This study therefore aims to determine the extent to which different psychiatric symptoms during adolescence predict body dysmorphic symptoms in adulthood.

Higher education attendance has important implications for individual’s future outcomes with those who attend higher education having higher earnings on average, as well as better health outcomes.
Attendance at higher education is already known to be affected by socioeconomic status, with those from lower socioeconomic backgrounds attending lower quality institutions and courses, relative to their attainment. However less is known about the role maternal depression may play in young person’s attendance at higher education and how it may influence their course and institution. Maternal depression has previously been shown to affect development and wellbeing with maternal distress being associated with worse socioemotional development, as well as being associated with worse educational attainment. This research will build on this existing knowledge by exploring the influence maternal depression has on higher education attendance.

The global burden of atopic diseases, in particular atopic dermatitis (AD), is on the rise. While most research is focused on the medical outcomes, a more encompassing approach is needed to highlight the effect of AD on social outcomes which has implications on future interventions and social support.
1 in 5 children in the UK suffers from AD, and to date, data are rather conflicting regarding its effect on educational attainment. A previous study on Swedish men who underwent military conscription at ages 17-20 years showed an association with attending university but no significant association between AD and secondary educational attainment after adjusting for family-related factors. Another cohort study on Dutch children found no association between AD and school performance at age 11.

Since educational attainment predicts future health and wellbeing, it is important to investigate any potential association with AD. AD may impact educational performance due to a multitude of factors: itching, poor sleep efficiency, and the use of sedative antihistamines could lead to absenteeism or poor concentration. AD stigma and comorbidities could increase depression, psychological distress, and the risk of attention deficit hyperactivity disorder, which may also adversely impact educational outcomes in affected children.
Additionally, neither have previous studies explored the effect of AD on exam results nor addressed the effect of the three main atopic diseases (AD, Hay fever, and Asthma) simultaneously. These diseases often co-occur, and it is important to determine the interplay and broader effect of atopic diseases on educational outcomes.

In a recent Mendelian Randomisation (MR) study we found a casual link to suggest an independent positive impact of staying in school on wellbeing, but a negative impact of intelligence on wellbeing. In the current project, we aim to explore further the extent to which either of these effects are moderated by the other. To do this, we will use available data from genome-wide association studies (GWAS) on educational attainment and intelligence to construct polygenic scores. These scores will be used in an interactive model to predict wellbeing in ALSPAC participants. This will allow us to investigate whether the positive effects of educational attainment are driven by those with higher intelligence, and whether negative effects of intelligence are moderated by spending more time in school. We also aim to understand more about the factors driving the main effects of educational attainment and intelligence on wellbeing. We will therefore investigate the potential role of socioeconomic status (SES), personality, and peer relations. Previous findings have shown that children more likely to complete more years of schooling tend to grow up in families with more socioeconomic resources (Krapohl & Plomin, 2016), have certain personality traits (Heckman, Stixrud & Urzua, 2006), and more extensive social networks (Chen, 2012). Thus, we aim to explore the extent to which these factors mediate or moderate associations between educational attainment and wellbeing, and between intelligence and wellbeing.

Multiple studies have found an association between decline in lung function and cognitive ability in later life such as memory and problem solving, but the relationship in childhood remains unknown. If an independent association between lung function and cognitive ability can be identified, the possibility arises that interventions to reduce pre-birth or early life risk factors for poor lung function could improve children’s life chances.

Children born with a cleft (gap) in the lip and/or palate face tough challenges throughout their lives. They undergo multiple operations and attend numerous clinical appointments, creating significant stress on children and their families. Many children experience facial disfigurement and difficulties making themselves understood, which can lead to teasing and low self-esteem. These children are particularly vulnerable to mental health issues, but it’s currently unclear how many children are at risk and how to identify them. With the COVID-19 pandemic introducing additional difficulties with delaying surgeries and disrupting schooling, we urgently need to develop a better understanding of which children are likely to need additional psychological support. Therefore, this research project aims to shed light on the pathways linking clefts to mental health problems. We will capitalise on our existing access to large-scale population-wide and clinical cohort studies, including the Cleft Collective cohort study, which is the world’s largest and most detailed longitudinal cohort study of children and families affected by cleft. In this established cohort, we will send additional questionnaires to collect more information as the children grow up and enter puberty, which is when mental health problems tend to emerge. Using these data, we will provide the first detailed description of mental health outcomes in children born with a cleft, and compare this to the same outcomes in children without a cleft IN THE ALSPAC COHORT and the Millennium Cohort Study. We will use state-of-the-art statistical approaches to study the contribution of genetic and environmental factors to shaping mental health in children born with a cleft, and we will use data from the Cleft Collective cohort study’s COVID-19 questionnaire to study the impact of the pandemic on these particularly vulnerable children, many of whom experienced delays in their surgeries. Finally, we will use our existing strong links to the NHS cleft teams and cleft charities to feed our findings directly into clinical decision making and policy to enable clinicians to plan provision to improve mental health outcomes for these children.

The menopause is a significant event in the life of any woman, marking the end of their reproductive life. However, the timing of the menopause is not only associated with the end of fertility, but also the increased risk of mortality and developing serious morbidity, including cardiovascular disease; osteoporosis; and breast and endometrial cancer (Carty et al., 2013). Previous studies have concluded that the heritability of the age at natural menopause (ANM) is approximately 30-90% (Murabito, Yang, Fox and Cupples, 2005; Murabito, Yang, Fox, Wilson, et al., 2005; Long et al., 2006); therefore, understanding the precise pathways, genes and individual polymorphisms that affect the ANM, and therefore the risk of developing menopause-related disease, is important. The DNA damage response (DDR) pathway, and many genes within it, has been identified in several genome-wide association studies as significantly linked to the timing of the menopause (Stolk et al., 2012; Chen et al., 2014; Day et al., 2015; Wang et al., 2019). The mechanism behind this is theorised to be an increased rate of follicular atresia due to accumulating DNA damage, leading to earlier menopause in women with mutations that reduce the efficiency of genes within the DDR pathway (Stolk et al., 2012; Titus et al., 2013; Perry et al., 2014; Day et al., 2015).
Menarche is another reproductive milestone within a woman’s life, and the age at menarche (AAM) could theoretically influence the ANM (Parazzini, 2007). The duration of the reproductive years - between the AAM and ANM – is associated with oestrogen exposure which can increase or reduce the risks of developing certain diseases, such as atherosclerosis (Cui et al., 2006).

In this project, we aim to investigate the associations between single nucleotide polymorphisms (SNPs) within genes of the DDR pathway and the ANM and AAM in mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC). This will form part of the research project component of my MSc degree in Reproduction and Development at the University of Bristol.
This proposal forms the basis of a multidisciplinary, collaborative MSc student research project which is being jointly supervised by research groups in Population Health Sciences and Translational Health Sciences, and financially supported by the MSc in Reproduction and Development within the Bristol Medical School. As part of this postgraduate taught MSc (https://www.bristol.ac.uk/study/postgraduate/2021/health-sciences/msc-re...), the 60-credit research project encompasses a student-led topic of interest, composed of a detailed literature review and a novel research dissertation which can be in the form of a data analysis project (this proposal) or a paper-based project.
As such, data extraction will be performed by an ALSPAC direct user (Kimberley Burrows) and this dataset will be sent to the ALSPAC data team for ID recoding prior to forwarding on to the primary analyst (Alex Shattock, RED MSc student 2020-21).

References
Carty, C. L., Spencer, K. L., Setiawan, V. W., et al. (2013) ‘Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study.’, Human reproduction (Oxford, England), 28(6), pp. 1695–1706.
Chen, C. T. L., Liu, C.-T., Chen, G. K., et al. (2014) ‘Meta-analysis of loci associated with age at natural menopause in African-American women.’, Human molecular genetics, 23(12), pp. 3327–3342.
Day, F. R., Ruth, K. S., Thompson, D. J., et al. (2015) ‘Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.’, Nature genetics, 47(11), pp. 1294–1303.
Cui, R., Iso, H., Toyoshima, H., et al. (2006) ‘Relationships of age at menarche and menopause, and reproductive year with mortality from cardiovascular disease in Japanese postmenopausal women: the JACC study.’, Journal of epidemiology, 16(5), pp. 177–184.
Long, J.-R., Shu, X.-O., Cai, Q., et al. (2006) ‘Polymorphisms of the CYP1B1 gene may be associated with the onset of natural menopause in Chinese women.’, Maturitas, 55(3), pp. 238–246.
Murabito, J. M., Yang, Q., Fox, C. S. and Cupples, L. A. (2005) ‘Genome-wide linkage analysis to age at natural menopause in a community-based sample: the Framingham Heart Study.’, Fertility and sterility, 84(6), pp. 1674–1679.
Murabito, J. M., Yang, Q., Fox, C. S., Wilson, P. W. F., et al. (2005) ‘Heritability of age at natural menopause in the Framingham Heart Study.’, The Journal of clinical endocrinology and metabolism, 90(6), pp. 3427–3430.
Parazzini, F. (2007) ‘Determinants of age at menopause in women attending menopause clinics in Italy’, Maturitas, 56(3), pp. 280–287.
Perry, J. R. B., Hsu, Y.-H., Chasman, D. I., et al. (2014) ‘DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.’, Human molecular genetics, 23(9), pp. 2490–2497.
Stolk, L., Perry, J. R. B., Chasman, D. I., et al. (2012) ‘Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.’, Nature genetics, 44(3), pp. 260–268.
Titus, S., Li, F., Stobezki, R., et al. (2013) ‘Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans’, Science translational medicine, 5(172), p. 172ra21.
Wang, G., Lv, J., Qiu, X. and An, Y. (2019) ‘Integrating genome-wide association and eQTLs studies identifies the genes associated with age at menarche and age at natural menopause.’, PloS one, 14(6), p. e0213953.

Typical analysis of genetic data to find a gene with a risk for a disease is designed to look for single gene/allele relationships. While multiple relationships can be found they assume independence. We have developed novel methods that assess allele-allele interactions. Normally in biology genes interact and abnormal changes in gene expression or functions in two or more members of an interacting set of genes may lead to disease. OUr novel methods can build netwoks of allels that combine to increase risk of preeclampsia and potentially other diseases of pregnancy.

Selection bias is pervasive in human studies and even more so for epigenome-wide association studies (EWAS) due to the relatively high costs of measuring DNA methylation. Although this bias is often acknowledged, its impact on findings has not been evaluated. We aim to perform such an evaluation for EWAS performed in ALSPAC. We will characterise selection by comparing the characteristics of ALSPAC participants measured at baseline with and without DNA methylation profiles and then estimate the resulting bias using simulations informed by the data.