Several longitudinal cohort-based studies have shown that the onset of various psychiatric disorders in adulthood are often preceded by psychiatric symptoms and disorders in childhood and adolescence (Kessler et al., 2007, Rao and Chen, 2009). Similarly, childhood psychopathology has been found to be associated with physical traits including BMI, as well as adversely affecting cognitive traits like IQ and educational attainment (Pine et al., 2001, Singh et al., 2013, Costello and Maughan, 2015). These individuals typically go on to have less favorable outcomes in areas of adult functioning related to health, SES and social relationships/isolation (Copeland et al., 2015, Costello and Maughan, 2015).
The goal of this project is to carry out large-scale analyses of the genetic overlap between adult psychiatric disorders and related traits, and childhood and adolescent psychiatric phenotypes. To achieve this, this study will use available GWAS summary statistics data on adult psychiatric disorders and related traits to construct polygenic risk scores (PRS), as well as phenotype data on childhood internalizing behaviour, ADHD/Attention Problems and Social Problems from multiple suitable cohorts. Specifically, we will test the ability of the PRS to predict childhood and adolescent psychopathology in a regression model that tests the association between each polygenic score and each trait at different ages, thus allowing us to test for differences in the associations between different PRS and childhood psychopathology across cohorts, outcomes and age.
Summary results will be transferred to the analytical team in Amsterdam who will meta-analyse the ALSPAC data along with several other cohorts from the CAPICE consortium.

Glycosuria is a common disorder of pregnancy characterised by the presence of glucose in urine. Glycosuria may be caused by an increase in blood glucose such that the renal tubules are overwhelmed and complete reabsorption of presented glucose is not possible, a benign lowering of the renal threshold, or inhibition of renal tubule reabsorption 1,2. Primarily a result of a lower renal threshold, which is a consequence of increased renal blood flow, glycosuria during pregnancy may be a product of gestational diabetes and shows evidence as an indicator for later life adversity such as offspring risk of obesity 1,3.

Genes predisposing to type 2 diabetes have been associated with gestational diabetes 4 and there is growing evidence that impaired glucose regulation in pregnancy, including glycosuria, is associated with negative metabolic outcomes for offspring such as non-alcoholic fatty liver disease 5. Patients who develop gestational diabetes are at increased risk of gestational diabetes in future pregnancy, as well as being at risk of developing type 2 diabetes over the life-course 4. The presence of glycosuria may indicate future adverse outcomes in pregnancy and the life-course. To identify genetic variants associated with such a phenotype and to provide greater understanding of disease development, progression, and related complications we will set out to conduct a genome-wide association study (GWAS) of glycosuria during pregnancy, and investigate the genetic overlap between identified loci and multiple diabetic-related traits.

1. Lawlor, D. A. et al. Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort. Diabetologia 53, 89-97, doi:10.1007/s00125-009-1560-z (2010).
2. Ferrannini, E. Learning From Glycosuria. Diabetes 60, 695-696, doi:10.2337/db10-1667 (2011).
3. Patel, S. et al. Associations of Gestational Diabetes, Existing Diabetes, and Glycosuria With Offspring Obesity and Cardiometabolic Outcomes. Diabetes Care 35, 63-71, doi:10.2337/dc11-1633 (2012).

We all perceive the sensory world around us differently. Some autistic children for example are overwhelmed by sounds or touch. This can make everyday situations such as visiting a busy supermarket a challenging task for families. Being overly sensitive has also been linked to anxiety. This project will explore if sensory reactivity, such as being oversensitive to sounds, can predict later anxiety and related mental health symptoms. To do so we would analyse already collected ALSPAC data on sensory reactivity and mental health symptoms from 6 months of age onwards. This includes already collected caregivers questionnaires about how their child reacts to the sensory world around them, such as sounds and lights, and questions about anxiety. That way we can test if the relationship between sensory reactivity and anxiety and related mental health issues is stable over time. Also we can test if early sensory reactivity can predict later mental health symptoms. Identifying whether sensory reactivity predicts mental health symptoms over time could lead to a clinical impact. If sensory reactivity symptoms such as being oversensitive to sounds are identified and treated earlier, it might be possible to reduce the impact of subsequent mental health problems, such as anxiety. Last, this project will allow us to investigate genetic underpinnings of sensory reactivity and identify potential biomarkers for sensory reactivity issues, such as hyper-and-hypo reactivity.

Genes help determine whether an individual is left- or right-handed, but the genes that contribute to handedness are mostly unknown. The goal of our study is to identify genetic factors that determine handedness by comparing genetic information from left- and right-handed individuals. We also plan to compare genetic data for handedness to data from other traits and diseases to determine whether handedness is correlated with later risk of disease.

The health of pregnant mothers can influence the health of her offspring across their entire lifespan. In high income countries, as many as 1 of every 10 mothers experiences diabetes during pregnancy. The impact of exposure to diabetes during pregnancy on the heart health of offspring is poorly understood. We recently found that individuals exposed to diabetes in the womb were 2-3 times more likely to develop high blood pressure and heart disease in their teens and early 20s, compared to individuals not exposed to diabetes in the womb. We want to determine if this is something we can detect in childhood or adolescence and possible reasons why maternal diabetes could predispose children and adolescents to high blood pressure and heart disease later in life.

Despite increasingly gender egalitarian ideals, remarkable gender gaps persist in children’s early development and subsequent education, labour market and family choices. The question as to what extent biological factors, such as (prenatal) sex hormones, moderate or set a limit to social influences has received growing attention over the past decade. Yet our understanding of these relationships remains patchy and much remains to be explored. This project takes an interdisciplinary approach and integrates theoretical perspectives from sociology, social and clinical biopsychology and neuroscience. To-date, the number of empirical studies, which considered at least one measure of sex hormones and at least one set of socialisation factors or applied other innovative designs to shed light on the interaction of hormonal and socialisation influences, are limited (e.g., Berenbaum, Bryk and Beltz 2012; Davis and Risman 2015; Hines et al. 2002; Udry 2000). Drawing on the Avon Longitudinal Study of Parents and Children (ALSPAC), we will investigate how prenatal sex hormones and gendered parental environments and role modelling influence children’s interests in school subjects at different ages and the gender (a)typicality of their occupational aspirations and actual choices during adolescence and young adulthood. We extend the current literature by using prospective reports by parents and children over longer periods from early childhood to young adulthood. The findings will contribute to a better understanding as to what extent malleable environmental conditions may be more or less effective in altering gender differences in children’s identities, academic and occupational aspirations and choices.

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.

Cannabis is the most commonly used illicit drug in the US, with 14% of Americans aged 12 or older reporting use during 2016 and 44% reporting lifetime use. Both acute (e.g., impaired motor function) and chronic health effects (e.g., dependence, cognitive function) of cannabis use have been reported. However, efforts to assess the scope of the adverse effects are hampered by under-reporting and the lack of available biomarkers which can reliably quantify cannabis usage patterns. Thus, there is a need to develop robust biomarkers of exposure to more accurately identify usage patterns in order to monitor those in treatment for adherence, fill-in missing cannabis use history, and/or predict health consequences. DNA methylation (DNAm) represents an excellent candidate for biomarker research, as it has the potential to differentiate acute vs. chronic exposure, timing of exposure, and cumulative exposure.

The overarching goal of the study is to identify the first reliable and useful blood-based DNAm biomarkers for cannabis use phenotypes. To achieve our goal, we propose to leverage the ALSPAC study, along with existing data from ~7 other cohorts to conduct the largest epigenome-wide (genome-wide DNAm) meta-analysis for any cannabis use phenotype to date (N~10,000 individuals across cohorts). From this, will identify and validate DNAm biomarkers of cannabis use representing general biomarkers (i.e., without regard to the etiology of the DNAm differences, possibly providing the greatest overall predictive ability), and those enriched for either exposure- or genetically-driven effects (i.e., DNAm as a mediator between genetic variants and cannabis use).

Obesity, happiness and smoking patterns are among some of the phenomenon that seem to be influenced by an individual’s social network, exhibiting a “three degrees of influence” property. Transmission of gut bacteria could be a potential mechanism for transmission of genetic traits from one individual to another. Hence, it could potentially provide a plausible mechanistic explanation for some of the social patterns transmitted within social networks. Understanding the extent of gut microbiome transmission can help us elucidate some of social patterns that we observe in the human population.