There is strong epidemiological evidence to suggest that paternal postnatal depression (PPD) is associated with adverse offspring developmental outcomes in early childhood. However, few large prospective longitudinal studies have examined whether these adverse outcomes persist into later childhood (7 years of age). Furthermore, the offspring outcomes are heterogenous and effect sizes are small to moderate. Thus, it is important to elucidate putative mechanisms, i.e. mediating factors, that underly associations between PPD and offspring adverse developmental outcomes. Such insights are crucial to highlight those at greater risk and develop targeted interventions to reduce adverse outcomes in offspring of depressed fathers. A substantial body of evidence suggests that an important potential mediator is the quality of parenting. Specifically, evidence suggests that PPD disrupts paternal levels of involvement with the offspring and quality of parenting (e.g., bonding, enjoyment, confidence), which, in turn, is associated with adverse offspring outcomes, including emotional and behavioural problems. However, few population-based studies have examined potential explanatory role of fathers’ involvement and parenting in the association between PPD and offspring development using longitudinal mediation models.

ALSPAC is well-placed to contribute to the national/international Covid-19 research effort given it has an extensive archive of data about participants health and wellbeing and circumstances prior to the Covid-19 outbreak and is now collecting data specifically related to Covid-19. These data can be used with our biobank and genetic data.

This project seeks to enhance these data with NHS and other Covid-19 records. These will bring timely information about symptoms, help-seeking and care and disease outcomes. It will allow ALSPAC to look at Covid-19 specific health (i.e. the health of those with the virus) and wider general physical and mental health (which may be impacted by stretched NHS resources during the outbreak, or due to the 'lock-down' and social distancing).

This data will sit alongside the other health records ALSPAC have collected. The same security mechanisms will be used to keep the data confidential, and ALSPAC will not extract records from participants who have objected to this use of their data.

The records will be sourced from:

1) A new NHS national (English) repository of Covid-19 data (GP records, Hospital Records, Pharmacy data, NHS 111 call records, Ambulance Records, Mortality Records, Covid-19 testing records).
2) Respiratory care records from databases at NHS University Hospital Bristol Trust and NHS North Bristol Trust hospitals.
3) Records from the 'Zoe' symptom tracker app.

ALSPAC will immediately use the data to help understand more about the factors that influence the susceptibility and severity of Covid-19. We will also examine whether Blood Group and the FUT2 gene (and other genes) are associated with Covid-19 susceptibility.

The Diabetes and Metabolism Unit at Southmead has a long history of measuring antibodies. Over the last three years we have focused on a particular type of assay which works on very small samples of blood. We have also good systems for sending small tubes by post which allow people to take a small blood sample from their finger and post it safely back to the laboratory for antibody testing. Since the recent COVID-19 pandemic we do not know how many people have been infected by the virus and this is a very important question. We have been working closely with a research group in Milan who have developed a test to work out who has been infected with Covid-19 because they have antibodies to the virus. Initial tests suggest that this assay works well on very small blood samples. We are now setting up this assay in Bristol and are requesting to access some samples from ALSPAC for
1. a University of Bristol study to test different assay platforms using the same samples
2. to prospectively and safely collect low volume samples by post and use the assay to estimate the infection rate in the general population and link this to questionnaire based data regarding symptoms.
This study should allow us to work out quickly and reliably how many people in the ALSPAC population have had COVID-19.

School closures have been a central component of many countries’ response to contain COVID-19; however, we don’t know:
• What children do during unplanned school closures
• Whether children are infectious
• Whether other strategies could be equally effective.
Much of the policy is based on influenza, which does affect children more than SARS-CoV-2 [1].

Preliminary evidence suggests that children are able to become infected with SARS-CoV-2, but are either asymptomatic or show mild symptoms, with a minority of cases progressing to disease [2]. The role of healthy children in transmitting SARS-CoV-2 remains uncertain. It is of interest to define how many children do/don’t experience COVID-19 symptoms and have evidence of having had SARS-CoV-2 infection, this may have implications for transmission dynamics and policy decisions. Along with many European countries, the UK decided to close schools from March 23rd in an effort to slow SARS-CoV-2 transmission - only some vulnerable children and those of key workers remain in school. We do not know what children’s contact patterns are during this unplanned school closure, but there is evidence that contacts inside and outside the home might continue, especially for older children and where parents don’t agree with closures [3]. We propose to deploy a survey to G2 ALSPAC children to capture data on symptoms and contact patterns during the COVID-19 pandemic, as well determine evidence of SARS-CoV-2 infection through saliva antibody detection methods.

Alcohol is the leading cause of ill-health in young adults in the UK and Europe and is the fifth leading cause across all ages in the UK population and is estimated to be the seventh leading cause globally . There are over 1 million alcohol related hospital admissions and nearly 25,000 alcohol related deaths a year in England with trends, in stark comparison to other major causes of death, not yet decreasing.

Since our previous grant (ALSPAC Alcohol at 24) there have been several important changes to our understanding of the risks of alcohol, patterns of drinking in the population, and UK response to preventing alcohol related harms.

First, levels of drinking reported by adolescents in UK and many other countries have fallen, corresponding with a fall in alcohol related hospital admissions in those under 18, but not yet resulting in any measurable decline in alcohol related harms in young adults . The motivation, reasons (and potential modifiable factors) causing the decline are not yet known but under investigation. In adults in the UK there is some evidence that changes in alcohol use has been differential with greater reductions in low level drinkers and no change in heavier drinkers with subsequently little overall impact on alcohol related harms. At the same time harmful alcohol use has been recognised as an important contributor to the “deaths of despair” that have reduced life expectancy – especially among poorer and more marginal populations - in North America.

Second, in large well powered genetic studies (and against decades of observational data) the cardio-protective effect of alcohol has been shown to be false – and instead likely to be due to non-causal factors all along (such as confounding, selection bias and reverse causation). This implies that there is no compensation of low levels of alcohol use improving morbidity and mortality and no absolutely “safe” or “non-risky” levels of drinking – and clear benefits from reducing average consumption. The UK in line with other countries issued new guidelines on safe drinking levels – which are now the same for men and women – though evidence is unclear whether there have been any changes in the UK population as a result of the new guidance. Policy changes also are underway – notably in Scotland - based on economic models that show how introducing and raising minimum price of alcohol can reduce future alcohol related morbidity and mortality. [There have been other advances in use of MR and genetic markers to identify new targets for drug discovery, compare the impact of interventions, and test for interactions between behavioural exposures – but in European populations MR of alcohol use and AUD have been limited by lack of robust markers.]

Third, it is argued that alcohol related health harms may be under-estimated in part because cohort studies under-represent heavier drinking marginal populations but also because of an under-appreciation of the interaction of alcohol with other exposures. The burden of alcohol is greater in poorer communities, alcohol combines with other exposures to increase risk of liver disease, and alcohol can act as a “snare” increasing the persistence and halting the resolution of antisocial behaviour. This has led to a renewed focus on understanding how adverse alcohol trajectories develop and interact with other exposures to increase health and social harms to strengthen the evidence base ultimately for policy-makers but also for alcohol policy models that can show the impact of alternative prevention strategies.

The coronavirus (COVID-19) pandemic has had and will continue to have an unprecedented effect of daily living for the foreseeable future. Aside from the obvious effects of COVID-19 on physical health, this pandemic is also likely to have a profound effect on mental health. The knock on effects on mental health could be far reaching and long term especially if not understood and managed.

In addition, it is likely to exacerbate existing inequalities and the costs are likely to be felt disproportionately to the already most vulnerable ( those with a history of mental illness, job and housing insecurity , poor neighbourhoods , single parents and those in abusive relationships).

A number of rapid surveys have indicated an initial perceived rise in depression and anxiety symptoms. However, without pre-pandemic information, an accurate indication of the change is not possible. This is essential for modelling projected risk which needs to be taken into account when planning further policy regarding social distancing and lock down enforcements.

Longitudinal data is thus crucial. It is also important to identify at risk groups who could benefit from immediate help and planning for currently unknown policies for recovery stages. This project will use the unique data hosted by ALSPAC to examine how and why mental health changes as a result of the public health policies adopted during the COVID-19 pandemic.

Data collection

Epilepsy is a neurological disorder that affects one percent of the population. Genetic factors play a role in epilepsy, but the full spectrum of the genetic architecture for this disorder is unknown. Previous work indicates that rare variation may contribute to epilepsy risk, but large sample sizes are required to increase the likelihood of identifying new risk genes or variants. The goal of this project is to investigate the genetic components of epilepsy in a large, well-characterized epilepsy cohort, in collaboration with Epi25, a consortium of over 50 epilepsy investigators. Whole exome sequencing (WES) data from epilepsy samples generated at the Broad Institute will be analyzed with ALSPAC WES data and other locally available or dbGaP-sourced controls to identify genes or variants associated with epilepsy. The inclusion of the ALSPAC data will be a valuable contribution to increase power in downstream analyses.