Radon is a colourless, odorless and tasteless gas that occurs naturally in rocks and water. It is also a radioactive decay product of radium. Inhaled radon gas is the main contributer to ionizing radiation in the general population. Although it occurs naturally, this differs depending on the make-up of soil while it can also accumulate in buildings (especially in low areas). Epidemiology has shown a clear link between radon gas exposure and lung cancer risk, including in non-smokers, and is considered the second most frequent cause of lung cancer (after cigarette smoking). In this project we, for the first time, will explore whether there is any evidence of epigenetic (DNA methylation) signals as a result of residential exposure to radon that can already be measured at young age (well before the development of lung cancer) and whether any signal could be dose-dependent. If there is evidence of such an association in ALSPAC, and given the ubiquitous exposure but also straightforward methods for interventions to improve the indoor environment, this project may result in (a) updated advice on hazards of radon exposure across the lifecourse and (b) a grant application to investigate this in a much larger cohort, such as the pooled cohorts in the CLOSER consortium), to provide more robust estimates of risk.

Craniofacial morphology has been classified in a 15-year-old population (Toma et al, 2012) and similar facial phenotypes in Twins UK were also found to be highly heritable (Djordjevic et al, 2016). The findings of these studies will inform further research to derive additional genetic variants that influence normal facial variation in the general population. The Bristol and Cardiff collaboration were the first to report the PAX3 gene in a normal population. This gene influences the prominence of the nasion (bridge of the nose) (Paternoster et al., 2012). Since this paper was published, there have been significant advances in using dense surface facial meshes rather than landmarks to derive facial phenotypes creating robust analyses that will identify genetic variants for facial morphology which can shed light on the risk factors for facial dysmorphologies and abnormalities, such as cleft lip. The student will have the opportunity to collaborate with Visigen, an international consortium of experts on visible trait genetics, to take part in large scale genomic analysis of facial morphology.

Members of the ALSPAC cohort (mothers, fathers and their offspring) have been followed up for almost 25 years through regular questionnaires and clinics. ALSPAC aimed to recruit all eligible mothers during their pregnancy – however, there may be some differences between participating and non-participating mothers in terms of social and lifestyle characteristics. Other studies which are used in medical research may be less representative of the general population, and this may lead to biased results. However, for each study, it is hard to identify differences between those who participate and those who don’t, as we only have information on those who participate. In this research we will use genetic variants that are associated with lifestyle factors, for example, education, body mass index and smoking, to assess whether the distributions of each of these factors differ between participants in the ALSPAC study and participants in other studies which may be less representative of the general population. We will also examine differences between participants in ALSPAC and participants in the ARIES substudy, where we know some of the lifestyle factors which differ between these two groups. Understanding whether we can identify factors related to participation from genetic data collected on participants will help researchers to obtain correct results in ALSPAC and in other cohort studies.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterised by impairments in reciprocal social interaction, communication, and restricted and repetitive patterns of behaviours and interests. The individual, familial and societal burden of autism is extensive. Depression, anxiety and suicidal behaviour and self-harm are often cited as some of the commonest co-morbidities in ASD, and may lead to additional impairment in quality of life and disability. However, the supporting data largely comprise small (typically under 100 individuals), selected samples and case series, often without a comparison group. The results are therefore difficult to generalise and estimates liable to selection bias and confounding. Since these morbidities are common in the general population, it is unclear whether autism, or any specific impairments related to autism, confer any additional risk to their development. Longitudinal population based studies following children into adulthood have been called for but have been absent from the literature to date. Beyond understanding the relative risk of adult mental health outcomes in individuals with autism, a bigger question is whether any risk or protective pathways could be identified. Such information would be invaluable to inform the development of public health interventions. As an illustrative example, bullying and victimisation, commonly experienced by children with ASD, may contribute to the future development of mental health problems. If this were true, targeting such ‘mediating’ pathways may help prevent adverse mental health outcomes in a proportion of cases, irrespective of our ability to modify core autistic symptoms.

We aim to conduct a comprehensive study using the complementary strengths of two large population based cohorts (Alspac and the Stockholm Youth Cohort) with prospective data to make substantial contributions to the major gaps in the research evidence in this area.

In the UK asthma is the commonest chronic illness of children, but attempts to prevent childhood asthma have been largely unsuccessful. Epidemiological studies have suggested that exposure of a child before and after birth to tobacco smoke and air pollution increases their risk of developing asthma. A low consumption of fruit and vegetables and antioxidant vitamins (vitamins C, E and A) early in life may also increase risk. In the ALSPAC study we recently discovered that children with particular types of a gene called TRPA1 were more likely than children with other types of the gene to develop asthma. The TRPA1 gene controls a protein which is thought to increase inflammation of the airways in asthma, and the action of this protein is increased by harmful substances in the environment, such as tobacco smoke and air pollution.
We believe that children with ‘risky’ forms of the TRPA1 gene may be more likely than other children to develop asthma when they are exposed early in life to tobacco smoke and air pollution, or if their intake of protective antioxidants (from fruit, vegetables and vitamins) is low. We plan to test this hypothesis by analysing existing data in ALSPAC. In a subset of ALSPAC mothers and children we will also explore whether the risk of developing asthma partly depends on whether the TRPA1 gene is turned on or off. We will do this by measuring how much the DNA in the TRPA1 gene is chemically altered by a process called 'methylation'. Exposure to pollutants can alter the level of DNA methylation and this, in turn, can influence the extent to which a gene is turned on or off.
If we can confirm that infants who carry ‘risky’ forms of the TRPA1 gene are more likely to develop later asthma when exposed to harmful pollutants or a poor diet, this could help us to find ways to prevent childhood asthma from developing in the first place in these vulnerable individuals. For example, infants who are genetically susceptible in this way might particularly benefit from taking antioxidant vitamin supplements or from strategies designed to reduce their exposure to air pollution.

Anxiety is associated with alcohol use. However, different hypotheses exist regarding the direction of these associations and evidence is inconsistent. Following on from a recent experimental study which found that state anxiety leads to higher alcohol choice, this epidemiological study will investigate the relationship between adolescent anxiety and alcohol use in young adulthood.

The Genetic and Epigenetic factors of Endothelial function and Chronic Pain

ALSPAC can collect information on participants life events through linking to their routine administrative records held by UK government. These are the records that all of us build up as we use government services (such as school records or GP records) or interact with government in other ways. For some participants, this will include records of criminal convictions and cautions. As part of ALSPACs work to establish these linkages we have conducted a pilot exercise linking some participants to their Police National Computer (PNC) database records (see project B557 for this work). The result of this linkage was a completely anonymous dataset, i.e. it includes ALSPAC participants PNC records, but cannot be linked to the ALSPAC dataset. In this project we would like to conduct simple comparisons of criminal records in this pilot exercise with participant reported criminality information provided at focus clinic and in questionnaires. The evidence will help inform the development of our linkage strategy.

T1D is an unrelenting chronic disease of childhood that places a substantial burden on children and their families. This onus is increasing rapidly as the annual incidence rate of T1D is growing by ~5% per year in developed countries, such that by 2020 the number of children in Europe with T1D will increase by 70% from 2005 levels. T1D leads not only to a reduced lifespan by 12 years, but also to increased rates of renal failure requiring life-long dialysis, blindness, limb amputation, coronary heart disease and stroke. This study aims to use ALSPAC genotype data as controls in the replication of genetic association findings found to be associated with risk of T1D.