What is your Research Question
Can we enable research by producing and maintaining an up-to-date tool that summarises the tissue, longitudinal study data, archives and samples (‘resources’) in all viable UK collections and data harmonisation repositories? The combination of resources across multiple and complementary data/participant/sample sets can lead to substantial research contributions. The research resource landscape in the UK today ranges from the “macro” to the ”micro”, but where viable1, these different collections can be complementary in efforts to dissect important research questions. Learning from the experiences light touch, dynamic and responsive consortia, we seek to provide a shop window for resources which is comprehensive, automatically updated and facilitates impactful research.

Postpartum depression (PPD) is a common occurrence among women who have just given birth. It has serious consequences for both the woman herself, and her family. PPD can have short term impacts, which can include feeling depressed, having difficulty performing normal tasks at home or work, and loss of interest in her new baby. It can also have long-term impacts, particularly for the children of women who are experiencing PPD. Research suggests that PPD and other mental health disorders affecting women who have just given birth can have serious economic implications, potentially costing up to £8.1 billion annually if the impacts on the children are considered (Bauer et al., 2014).
Recent research (Netsi et al, 2018) assessed long-term outcomes for mothers and offspring related to PPD using the ALSPAC data and found that severe PPD that persists past 8 months after birth is associated with an increased risk of negative outcomes for children on a large number of measures. We aim to build on their findings by evaluating whether early PPD (defined as PPD that occurs at the end of pregnancy and through 2 months following birth but which may resolve before the 8 month mark) similarly impacts long-term outcomes for women who have just given birth, their partners, and their children. We hope to track the impact of PPD on the likelihood of later depression for parents and children, as well as behavioral problems, antisocial behavior, psychosocial disorders, and academic achievement for children. We will use multivariate modeling techniques to account for factors that may confound the association.

The placenta is a temporary organ that is essential for a healthy pregnancy, normal growth and development of the fetus, and hence birth of a healthy infant. Placental dysfunction increases the risk of pregnancy loss (stillbirth or miscarriage), hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, babies who are born too small or too large, death in the first year of life and cerebral palsy. We do not know how the placenta works. There are methods that can be used on placental tissue (collected after birth) to measure how the placenta works at a molecular level. However, it is not known how well these methods perform in large scale cohort studies like ALSPAC. The advantages of using these methods in cohorts like ALSPAC are that those studies have lots of information on the pregnancy and mother and child's health(which most studies that have used these methods do not). However, it is not easy in cohorts to collect placental tissue with the same rigour that has been used in placental research focused studies. In particular the time between delivery of the placenta and processing is suggested to ideally be 30 minutes, but this is not possible when placenta are being retrieved from hospitals and brought to a University laboratory like BBL. Whether longer time intervals make the measurements unreliable is not known. In this 'proof of concept' grant we will measure placental function at a molecular level by assessing gene expression, DNA methylation, and metabolites in detail using placenta from the ALSPAC-G2 cohort. We will assess how these measures relate to time interval between delivery and initial processing and undertake some preliminary research analyses.

The experience of maltreatment and neglect during childhood is among the strongest predictors for psychosis development later in life, but the underlying mechanisms remain subject of wide speculation. The overall goal of this project is to explore how parental genes that are not passed on to the child can help explain the association between adverse childhood experiences and psychosis through their contribution to the child’s environment.

A child’s exposure to a certain environment partially depends on the genes they inherit from their parents (for instance, genetic predisposition for risk-taking can affect the degree to which an individual seeks stressful life events). Importantly, we now know that genes of the parent that are not transmitted can nonetheless significantly shape the child through their impact on the parent’s behavior. This phenomenon, referred to as “genetic nurturing”, has typically been ignored in genetic studies, but may point to potential preventable exposures.

With increasingly powerful ‘genetic risk scores’ (i.e. the sum of risk genes that have shown to be associated with a disorder), we are now able to test the role of genetic nurturing in psychosis development.

Leveraging the Avon Longitudinal Study of Parents and Children (ALSPAC) study, we will be able to integrate genetic and developmental data on over 3,000 individuals that were followed up from birth up to age 24 - as well as their parents. This will give us the unique opportunity to examine the effect of genes that are not passed on to the child in the childhood adversity-psychosis relationship.

There is a large body of research validating self-report medical data with that obtained through linkage, for example (1–3). There is however far less research that has investigated the validity of educational data self-reports, with studies restricted to small samples (4) or single courses (5). The accuracy of official measures of education such as the UK national Pupil Database is cited as one of the main advantages to conducting data linkage in cohort studies, and therefore determining the accuracy of self-reports when compared to these official measures is of critical importance for assessing the benefits of data linkage. Furthermore, the direction and magnitude of mis-reporting has been found to vary with individual characteristics(5) which will means that measurement error will contain not just random noise but also directional bias.

ALSPAC holds data on G1 participants’ education via data linkage only. Retrospective collection of participants education through self-report responses to questionnaires would allow the accuracy of this data to be compared to the linked data. Given the rich data that ALSPAC holds on its participants it may also be possible to investigate how misreporting varies across a range of individual characteristics including sex, intelligence, and family socioeconomic position. We note however that this analysis into misreporting may be restricted due to the non-random nature of cohort attrition in ALSPAC. Below we highlight some of the research questions that could be addressed through the collection of self-report education data collected by ALSPAC.

The importance of this data collection is demonstrated by recent changes in data linkage surrounding data sharing. The NPD recently decided to temporarily withdraw all data linkage due to data sharing and confidentiality issues, highlighting the risk that because linked data is not owned by cohort studies it can be pulled at short notice. Collecting self-report education data will therefore also provide ALSPAC with a safety net in the form of its own accurate educational records in the worst-case scenario that NPD data linkage is revoked permanently. While this self-report data will be only a sub-sample of the cohort due to attrition, it will ensure a larger sample than collection at a future occasion due to continued attrition.

As part of this data collection we will clean, code and deposit all data with full accompanying documentation and code for use by others.

1. Hafferty, J. D. et al. Self-reported medication use validated through record linkage to national prescribing data. J. Clin. Epidemiol. (2018). doi:10.1016/j.jclinepi.2017.10.013
2. Comino, E. J. et al. Validating self-report of diabetes use by participants in the 45 and up study: A record linkage study. BMC Health Serv. Res. (2013). doi:10.1186/1472-6963-13-481
3. Mars, B. et al. Using Data Linkage to Investigate Inconsistent Reporting of Self-Harm and Questionnaire Non-Response. Arch. Suicide Res. (2016). doi:10.1080/13811118.2015.1033121
4. Sticca, F. et al. Examining the accuracy of students’ self-reported academic grades from a correlational and a discrepancy perspective: Evidence from a longitudinal study. PLoS One (2017). doi:10.1371/journal.pone.0187367
5. Rosen, J. A., Porter, S. R. & Rogers, J. Understanding Student Self-Reports of Academic Performance and Course-Taking Behavior. AERA Open 3, 2332858417711427 (2017).

The link between maternal smoking in pregnancy and asthma or wheeze in offspring is well-documented, but emerging evidence suggests that paternal smoking could also impact child health. This project aims to investigate to what extent paternal smoking in the prenatal period can causally affect childhood respiratory function, through a direct effect (e.g. via the male germline), or via an indirect intrauterine effect of maternal (passive) smoke exposure. Findings will help indicate whether or not fathers could be an effective (but currently understudied) target for interventions designed to lower the rate of childhood respiratory disorders.

Obesity is associated with a range of poor health outcomes (e.g., high blood pressure), but not all obese individuals have these outcomes. The relationships of childhood growth and body mass index (BMI is used to define obesity) trajectories, that describe how BMI changes as a person ages, with adulthood obesity have been well-documented. However, few studies have investigated whether there are multiple different patterns of BMI change over age that all lead to adulthood obesity but have different health outcomes. For example, it has been proposed that there are two main BMI patterns that lead to adulthood obesity. The first is characterised by being big at all ages due to a healthy combination of fat and fat-free mass, while the second is characterised by low or normal BMI in infancy and subsequently an unhealthy level of fat accumulation in childhood. It is hypothesised that the first pattern doesn't incur any adverse health consequences, while the second pattern does. This project aims to test this idea that there exist multiple different BMI patterns that lead to adulthood obesity and that they have different consequences for cardio-metabolic health. The same analysis in normal weight adults will help explain the BMI pattern that leads to some normal weight adults having poor health prospects.

This five year project will examine the biosocial lives of birth cohorts as forms of knowledge, sites of social practice and trajectories of participation. Whilst biosocial research, which is concerned with the interaction of biological and social factors, is not new it is being re-invigorated in an era of ‘post-genomics’. Epigenetic and other omic related fields of inquiry are revealing the vital role played by environment and social context for health outcomes by focusing on the biological consequences, pathways and mechanisms of social exposures during the life-course. This project will explore how and in what ways birth cohorts are technologies of and for biosocial research. Longitudinal studies that follow the lives of participants and their families have become central to identifying and understanding how the social ‘gets under the skin’, making them important but, as yet, under researched arenas in social science for examining the social practices, cultural contexts and consequences of biosocial research.

Taking six regional birth cohorts from internationally diverse contexts (including ALSPAC) as an object of and subject for ethnographic inquiry we will generate in-depth anthropologically rich comparative accounts of the dynamics between birth cohorts and biosocial research within the global north and south (including South Africa, China, Latin America and Europe). At the same time we will develop methodological innovation in using ethnography as an intervention on biosocial knowledge aiming to make a neglected social science research tool an essential component of interdisciplinary life-course research.

Two recent large studies of adults found over 200 positions on the genome where variation in blood DNA methylation was associated with body mass index (BMI). At the majority of these sites, the direction of estimated effect seems to be from BMI to methylation, rather than vice versa. It is still unclear how long individuals need to be "exposed" to higher BMI before the associated changes in DNA methylation are seen, and how changes in BMI over the lifecourse might be associated with DNA methylation.