The US National Toxicology Program’s systematic review of fluoride neurotoxicity has identified many studies reporting substantial loss of IQ from early life fluoride exposure. Several are mother-child cohort studies finding lowered IQ and increased risk of ADHD. ALSPAC provides an ideal data set to further examine the association between early life fluoride exposure and developmental neurotoxicity.

The ALSPAC cohort is expected to have relatively low fluoride exposure from drinking water because most of the recruitment area has concentrations below 0.2 mg/L. The main source of maternal fluoride exposure is expected to be diet, especially from tea. ALSPAC mother’s diet questionnaires indicate a wide range of tea consumption. Other exposure sources to be considered are fluoride supplements and dental products.

Neurodevelopmental outcomes to be examined include IQ scores; developmental, behavioral, and ADHD scores and diagnoses.

Covariates that may affect the neurodevelopmental outcomes or modify the effect of fluoride will be considered.

One proposed mechanism of fluoride developmental neurotoxicity is through impaired thyroid function of the pregnant mother so maternal thyroid hormone and iodine levels will be considered as modifying factors.

Several recent studies have found gene-fluoride interactions resulting in greater loss of IQ for children with certain genetic variants so those gene variants will also be considered as covariates.

The association of fluoride with lowered IQ or other neurodevelopmental deficits is of great public health importance. Millions of people have elevated fluoride exposure, through sources including drinking water, diet, and dental products.

Woman are more likely to develop chronic pain than men and this sex difference emerges at puberty. Periods also begin during puberty and are painful for many girls. Traditionally period pain has been dismissed as “normal” and something that girls need to learn to live with. However, it remains the leading cause of school and work absenteeism in adolescent girls and young women and it may be a risk factor for the development of chronic pain. Studies in adults with period pain have shown alterations in a variety of body systems relevant to pain. However we do not know if these are a cause or effect of period pain or whether they are seen in adolescents with period pain. This project aims to determine whether period pain in adolescence predisposes an individual to develop chronic pain in the future. We will also explore whether there are differences in pain-relevant systems in adolescents with period pain compared to those without to help us understand how it might increase the risk of chronic pain in the future. Finally we will look for risk factors present in childhood that are associated with period pain in the early years of having periods.

We hope that by having a better understanding of the role that period pain plays in the development of chronic pain and the risk factors for developing period pain itself we may be able to identify strategies to reduce the risk of both types of pain developing in teenagers and adult women.

Literacy is fundamental to a nation's social and economic prosperity, and poor reading skills can have lasting negative outcomes on individuals. Key to avoiding enduring deficits in reading skill is early identification of risk, and targeted environmental intervention at the individual and population level. To do this, a complete understanding of the causes of variation in reading skill is needed and this necessitates a biopsychosocial approach. Our research will harness breakthroughs in genetics that yield practical genetic risk measures for literacy and language skills. We will extend research in a novel way by combining molecular genetic data with longitudinal environmental predictors of communication skills. The intersection of these rich datasets will permit us to address challenging questions about the gene-environment interplay on reading skill and their consequences on child and adolescent mental health.

Recent studies have suggested that genetic variants associated with smoking behaviours may actually be influencing outcomes such as risk taking behaviours. This may pose a problem for analyses which assume that these genetic variants are associated with smoking behaviours and not with other outcomes. Therefore, it is important to ascertain whether this is the case. We aim to assess whether genetic variants for smoking behaviours are also associated with other outcomes. We have conducted analyses in a separate cohort (the UK Biobank) which provides evidence to support this. However, we want to replicate analyses to see whether this is also the case in a different sample (ALSPAC) where selection into the UK Biobank might be different in ALSPAC and where we can also test associations in children prior to smoking. Our results will help inform future studies using these genetic variants for smoking behaviours.

Levels of self-harm and suicide rates are rising among young people. Substance misuse is one of the leading causes of harm in young people. Evidence from population-based longitudinal studies suggests that many young people who self-harm in adolescence do not persist with these behaviours into adulthood, either due to a natural decline in the behaviours or as a result of intervention. Substance use, however, tends to naturally increase into adulthood, reflecting increasing social norms as people reach the legal age of alcohol use. Substance misuse and self-harm are thought to share characteristics, as both can be conceived as behaviour used to cope with difficult underlying emotions but which can both cause serious harm to the self. Indeed, in clinical samples, self-harm and suicidal behaviours are often comorbid, however, there is a lack of research into the co-occurrence of these behaviours among young people living in the community.

In this study, we will describe the comorbidity of self-harm/suicidal behaviour and substance use from age 16 to 24, in order to see how these behaviours and their co-occurrence change over time. We will look at comorbidities between self-harm/suicidal behaviour and alcohol use, cannabis use and use of other illicit drugs.

Understanding how metabolic problems develop is of fundamental interest to the people with age-associated diseases and their families and there is strong community interest in protecting young people from a life-long trajectory towards a diabetic or otherwise metabolically unfavourable future. In recent years, childhood obesity has emerged as an important phenomenon that is projected to increase the number of people with high cardiometabolic risk when the young generations grow old. In the first phase, we will describe how a population of children at risk will eventually develop cardiometabolic risk factors later in their life using unprecedented longitudinal datasets and sophisticated statistical techniques. If additional funding is achieved for the second stage, we will also investigate if the combination of genetics and childhood trajectories of development would allow us to identify the most susceptible individuals and thus ultimately provide the parents with the information that they can use to take preventative action. The lead investigator has developed a statistical framework that allows us to integrate multiple time points and multiple biomarkers simultaneously across partially incomplete datasets. Such a multi-decadal and multi-variable view of metabolic dysfunction is scientifically unique and we also expect to derive novel information about the diversity of metabolic trajectories within real-world human populations. This epidemiological information will be useful for public health policy makers who wish to mitigate the adverse health impacts due to the prevailing obesity-promoting environment. Our study will provide a detailed biochemical fingerprint of the trajectory that carries the highest risk for late-life diseases that can guide nutritional inputs and other life style factors within preventative strategies.

Experiencing abuse in childhood (i.e., physical, sexual, and emotional abuse) increases the risk of many adverse outcomes in adolescence and adulthood, including poor educational attainment. However, the mechanisms underlying the relationship between child abuse and poor educational attainment are less well understood. One possible explanation is that child abuse leads to increased mental health difficulties, which in turn causes disengagement and disinterest in school. Previous studies have evidenced that child abuse increases the risk of mental health difficulties in later life, including both internalising problems (e.g., depression, anxiety) and externalising problems (e.g., conduct disorder, ADHD). In turn, externalising behaviours have been associated with lower grades and increased rates of dropping out of school. Some evidence also suggests that internalising problems are related to worse educational attainment, but the findings have been inconsistent. Therefore, the current study aims to examine whether internalising or externalising problems mediate the relationship between child abuse and educational outcomes at age 16.

Unfavourable lipid profile (i.e. dyslipidemia) is an established cause of cardiovascular diseases (CVDs). In recent years, several CpGs sites have been found on lipid-related genes or associated with lipid profiles, supporting the hypothesis that DNA methylation (DNAm) could be involved in regulating these genes and their role in lipid-related diseases [1].

1.Hedman, A.K., et al., Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies. Circ Cardiovasc Genet, 2017. 10(1).

Chronic pain impacts almost every aspect of the lives of the young people who experience it, including sleep, social relationships, and family dynamics. In an educational context, the presence of chronic pain for young people has been associated with lower levels of attendance and school functioning, as well as possible reductions in measures of academic achievement such as school grades, keeping up with schoolwork, and perception of school achievement. Recent research has also highlighted the potential role that poor sleep or sleep disorders may play in compromised educational performance. Through integrating these two research threads, this study will examine the possibility that the impact of chronic pain on educational outcomes is mediated through disturbed sleep in young people who experience chronic pain relative to their pain-free peers. Firstly, the study will map out the characteristics of young people aged 17 with chronic pain in a UK educational context. Secondly it will examine whether young people with chronic pain at age 17 find it more difficult to achieve in school compared to their peers who don't experience chronic pain after we take into account a range of other factors such as gender, IQ, socioeconomic status, and special educational needs. Finally, this project will examine how factors such as loss of sleep contribute to this relationship.