Evidence has accumulated that the parents of children with intellectual disabilities are at increased risk of adverse mental health outcomes including depression and anxiety. Research in the field is currently attempting to explore the nature of this association, trying to identify which parents are most at risk and to what extent is the association confounded by the family environment, genetics and prior episodes of adverse mental health. The ALSPAC cohort has not been used to explore this research question so far and has substantial information on the family environment, parental mental health before and after the development of an intellectual disability in the child, maternal genetics and child behaviours. Such information may be useful for identifying modifiable targets for intervention or exploring which parents are most at risk.

Cardiovascular disease (CVD) is the primary cause of premature morbidity and mortality in type 1 diabetes, with this effect particularly pronounced in those diagnosed at a younger age. The magnitude of this problem has recently been starkly highlighted by findings from the Swedish National Diabetes Register, where patients diagnosed with diabetes between 1 and 10 years of age were found to have a 10× higher risk of future acute myocardial infarction compared to those diagnosed between the ages of 26 and 30 years, and over a 30× higher risk than the general population. These and other data suggest that adolescence may be a particularly crucial time in the development of future CVD complications in type 1 diabetes, and that effective intervention at this age may offer long-lasting benefits for cardiovascular health.

While compromised glycaemic control represents the major risk factor for CVD complications in type 1 diabetes, individuals living with the disease are also exposed to many other well-established and potentially modifiable risk factors faced by the population at-large. Obesity is a well-established causal driver of subclinical disease in the young, is known to track into adulthood, and therefore represents one of the major risk factors in early-life for future risk of CVD. Although individuals with type 1 diabetes have traditionally been considered to be a relatively lean population, recent evidence has shown that obesity rates in this group are now similar or possibly even higher than in the general population, with an alarmingly high prevalence in children and adolescents.

For the last 14 years, our group have tracked, genotyped, and extensively phenotyped a cohort of adolescents with type 1 diabetes; first as part of a randomised clinical trial (The Adolescent type 1 Diabetes cardio-renal Intervention Trial - AdDIT), and then as part of a long-term epidemiological study (AdDIT Follow-Up). We now wish to use this data alongside that collected over the same timespan in ALSPAC to address the following aims and objectives:

Increased adiposity and Type 2 diabetes (T2D) have both been associated with increased risk of developing certain cancers and are both becoming increasingly prevalent globally. Although adiposity, T2D and cancer share many risk factors, the biological pathways linking adiposity and T2D to cancer remain poorly understood.

Chronic low-grade inflammation, characterised by abnormal cytokine production, is associated with both adiposity and T2D. Observational studies have suggested that increased adiposity and hyperglycaemia associated with diabetes induce the production of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-6 which have key roles in cancer. This observation has led to the hypothesis that chronic inflammation might be a potential mechanism linking adiposity and T2D to cancer. However, due to the inherent limitations of observational research such as reverse causation and confounding, findings from observational studies need to be interpreted with caution. Furthermore, previous studies have used a single ‘baseline’ measurement of adiposity, T2D and inflammation and cannot fully account for the time-dependent variability in these measurements which may lead to a biased estimation.

Mendelian randomization is an analytical approach where genetic variants reliably associated with risk factors of interest are used as proxy measures to re-estimate the associations between an exposure and an outcome where some of the limitations of observational epidemiology are reduced. In this investigation, we would like to use genetic variants associated with adiposity, T2D and related glycaemic traits to investigate the estimated causal association between adiposity and T2D with inflammatory proteins (measured using the Olink inflammatory panel). We will also use longitudinal measures of inflammatory proteins to investigate whether the relationship between BMI/T2D with inflammation changes over time (across childhood and young adulthood) and potentially identify patterns in the relationship between BMI/T2D and inflammation which may be relevant to cancer development.

Incontinence – both urinary and faecal – is a common childhood occurrence. Whilst most children obtain daytime bladder control by 3-years, and night-time bladder control at 4-6-years, it is not uncommon for school-age children to experience some form of incontinence (1). Indeed, parents of 7 ½ year-olds in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort reported 15.5% experienced bedwetting, and 7.6% experienced daytime wetting. Incontinence can seriously undermine quality of life, and psychological distress may occur if children become aware that incontinence is unusual for children of their age and/or following negative reactions from family or peers (1). Further, 20-40% of children in attendance of continence clinics meet diagnostic criteria of at least one psychiatric condition (2).

It is commonly believed that issues with continence during childhood will resolve with age (3). However, epidemiological studies report 2-3% of adolescents experience urinary incontinence, and 1-1.5% experience faecal incontinence (3). There is also evidence that adolescents experience more severe forms of incontinence compared to younger children. Indeed, a cross-sectional study of 16,512 children in Hong Kong found a greater proportion of frequent bedwetting (≥3 wet nights/week) accompanied with daytime wetting and other lower urinary tract symptoms in 11-19-year olds compared to 5-10-year olds (4).

Incontinence in adolescence is particularly problematic because this is a sensitive time period in which identity and body image are formed, and peer acceptance is highly valued (1). The shame and stigma associated with incontinence may affect friendships and participation in social activities, which may in turn increase risk of developing psychosocial problems. Psychosocial problems during adolescence have been linked to future adverse mental health and social outcomes, including poor academic attainment, low self-esteem, depression, and suicidal behaviours (1,3).

Whilst some studies have investigated whether childhood incontinence is a risk factor for poor psychosocial outcomes in adolescence, few consider the impact of incontinence issues that persist beyond childhood. Further research is therefore required to investigate the relationship between continence issues in adolescence and adverse mental health outcomes.

1. Grzeda MT, Heron J, von Gontard A, Joinson C. Effects of urinary incontinence on psychosocial outcomes in adolescence. European Child and Adolescent Psychiatry. 2017 Jun;26(6):649–58.
2. Heron J, Grzeda MT, von Gontard A, Wright A, Joinson C. Trajectories of urinary incontinence in childhood and bladder and bowel symptoms in adolescence: prospective cohort study. BMJ Open. 2017;7(3):e014238.
3. Whale K, Cramer H, Joinson C. Left behind and left out: The impact of the school environment on young people with continence problems. British Journal of Health Psychology. 2018;23(2):253–77.
4. Yeung CK, Sreedhar B, Sihoe JDY, Sit FKY, Lau J. Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study. BJU International. 2006;97(5):1069–73.

Intimate partner violence and abuse (IPVA), refers to any behaviour within an intimate relationship that causes physical, psychological, or sexual harm to those in the relationship. There is evidence that IPVA in older adult relationships is associated with poor mental and physical health. However, very little is known about the effects of IPVA in young adult relationships, and particularly in UK populations and for physical health. The aim of this project is to estimate the association between IPVA during young adulthood and cardiovascular health in the following years, in the Avon Longitudinal Study of Parents and Children.

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 and by comparing different ethnicities. We propose to systematically map genetic influences on DNAm and to compare these genetic influences across ancestries.

Information can be obtained from ALSPAC (B number folder) or the UK LLC on request

Religion can often be recognized as a source of reassurance for those undergoing major or traumatic events in their lives, providing the understanding that these events have their place within the order of the larger universe (Berger, 2011). Hence the Marxist dictum of religion being the “opium of the people.” However, there is relatively little research done on the inversion of this dynamic, specific types of trauma can also have an impact an individual’s strength of faith (Leo et al., 2021). This is particularly prevalent with death related trauma, often witnessing death of a loved one or colleague could influence individuals to either further embrace their faith or weaken it (Fontana and Rosenheck, 2004; Morris Trainor et al., 2019). This is consistent with the shattered assumptions model that posits that those that have undergone trauma often change their world view to ‘accommodate’ their negative life events (Janoff-Bulman, 2002).

The relationship between traumatic life events and religion has been studied in detail by the scientific community, however, the nature and direction of the relationship is still a contentious topic. A review by Chen and Koenig in 2006 found that of the 11 papers in the review, one found no association, four found a positive association, three found mixed associations, and three found an inverse association (Chen and Koenig, 2006).

In these studies, we aim to investigate the relationship between RSBB and traumatic life events in both directions. To find how participants’ religious beliefs impact how they deal with trauma but also if different life events are associated with a change in one’s religiosity.

Berger, P.L. (2011) The sacred canopy: elements of a sociological theory of religion. Available at: http://www.myilibrary.com?id=591409 (Accessed: 9 March 2022).

Chen, Y.Y. and Koenig, H.G. (2006) ‘Traumatic Stress and Religion: Is there a Relationship? A Review of Empirical Findings’, Journal of Religion and Health, 45(3), pp. 371–381. doi:10.1007/s10943-006-9040-y.

Fontana, A. and Rosenheck, R. (2004) ‘Trauma, Change in Strength of Religious Faith, and Mental Health Service Use Among Veterans Treated for PTSD’, Journal of Nervous & Mental Disease, 192(9), pp. 579–584. doi:10.1097/01.nmd.0000138224.17375.55.

Janoff-Bulman, R. (2002) Shattered Assumptions. Available at: https://www.vlebooks.com/vleweb/product/openreader?id=none&isbn=97814516... (Accessed: 17 March 2022).

Leo, D. et al. (2021) ‘The Effect of Trauma on Religious Beliefs: A Structured Literature Review and Meta-Analysis’, Trauma, Violence, & Abuse, 22(1), pp. 161–175. doi:10.1177/1524838019834076.

Morris Trainor, Z. et al. (2019) ‘Death salience moderates the effect of trauma on religiosity.’, Psychological Trauma: Theory, Research, Practice, and Policy, 11(6), pp. 639–646. doi:10.1037/tra0000430.

We know that some people carry rare mutations that disrupt the normal function of critical metabolic pathways, leading to conditions such as obesity and/or diabetes. Genome sequencing studies are increasingly identifying such rare mutations. Using knowledge about the precise structure and function of the proteins encoded by these genes, as well as experimental data generated in the lab, we can determine which rare variants are likely to be disruptive.

After identifying mutations that disrupt protein function, we can use the wealth of data available in ALSPAC to determine how possessing a disrupted protein affects a persons growth and metabolism. This will allows us to infer the function of proteins in human physiology, and will identify new drug targets for metabolic diseases like obesity and diabetes.