Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

Click here to export results in Word format.

B3661 - The societal costs of exposure to child maltreatment and domestic violence and abuse - 30/11/2020

B number: 
B3661
Principal applicant name: 
Kevin Herbert | Primary Care Unit, Department of Public Health & Primary Care, University of Cambridge (United Kingdom)
Co-applicants: 
Professor Steve Morris, Professor Gene Feder, Dr Annie Herbert, Dr Abigail Fraser
Title of project: 
The societal costs of exposure to child maltreatment and domestic violence and abuse
Proposal summary: 

Child maltreatment (CM) and domestic violence and abuse (DVA) are highly prevalent violations of human rights, recognised as being responsible for significant adverse short- and long-term impacts on the health, wellbeing and life opportunities of affected individuals. Multiple common risk factors are known to exist for CM and DVA, contributing to a high degree of co-occurrence. (1–3)

Understanding how these adversities interact and quantifying their individual and combined impacts is key to deriving accurate estimates of the burden that CM and DVA impose, both on services and on the individual throughout their life-course. Previous estimates of the economic burden of abuse were focused on either CM or DVA in isolation, which may fail to fully account for the intersection of CM and DVA and the relationships between exposure to multiple adverse childhood experiences and poor health. (4,5)

Study aims:
1) To estimate the impact on life outcomes (e.g. physical and mental health, healthy behaviours, employment and earnings, welfare use) resulting from exposure to CM and/or DVA, and to investigate the how this burden varies with household CM/DVA co-occurrence. This will inform parameters for the development of a multi-sectoral, incidence-based societal cost model and cost-effectiveness models for evaluation of relevant interventions.
2) To perform a comparative analysis with outcomes estimated from the Australian Longitudinal Study on Women's Health (ALSWH). (6) This will enable investigation of commonalities or differences between the UK and Australian cohorts with respect to the impact on life outcomes from exposure to abuse.

1. Herrenkohl TI, Sousa C, Tajima EA, Herrenkohl RC, Moylan CA. Intersection of Child Abuse and Children’s Exposure to Domestic Violence. Trauma, Violence, Abus. 2008;9(2):84–99.
2. Appel AE, Holden GW. The Co-Occurrence of Spouse and Physical Child Abuse: A Review and Appraisal. J Fam Psychol. 1998;12(4):578–99.
3. Edleson JL. The Overlap Between Child Maltreatment and Woman Battering. Violence Against Women [Internet]. 1999;5(2):134–54. Available from: https://doi.org/10.1177/107780129952003
4. Hughes K, Bellis MA, Hardcastle KA, Sethi D, Butchart A, Mikton C, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Heal [Internet]. 2017;2(8):e356–66. Available from: http://www.sciencedirect.com/science/article/pii/S2468266717301184
5. Bellis MA, Hughes K, Ford K, Ramos Rodriguez G, Sethi D, Passmore J. Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis. Lancet Public Heal [Internet]. 2019 Oct 1 [cited 2020 Apr 17];4(10):e517–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31492648
6. Loxton D, Dolja-Gore X, Anderson AE, Townsend N. Intimate partner violence adversely impacts health over 16 years and across generations: A longitudinal cohort study. PLoS One [Internet]. 2017;12(6):e0178138. Available from: https://doi.org/10.1371/journal.pone.0178138

Impact of research: 
The estimates derived from this study will be used to inform multi-sectoral, incidence-based cost and cost-effectiveness models to quantify the combined lifetime societal costs associated with CM and/or DVA in families, and to evaluate the cost-effectiveness of relevant interventions. The development of these models, built upon the best available evidence will enable robust comparative evaluations of alternative interventions that aim to reduce either the occurrence or severity of CM or DVA. The models will thus provide a framework upon which decision-makers can explore the impact of implementing alternative policies and identify the most cost-effective methods for addressing the consequences of CM and/or DVA. The comparative analysis of the ALSPAC and ALSWH studies will provide insight into whether the impacts of abuse are generalisable between the UK and Australian populations. The findings of these analyses will thus have implications for the approaches that the respective nations may need to take to address the impacts of abuse.
Date proposal received: 
Wednesday, 18 November, 2020
Date proposal approved: 
Monday, 30 November, 2020
Keywords: 
Health Economics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Diabetes, Mental health, Obesity, Computer simulations/modelling/algorithms, Childhood - childcare, childhood adversity

B3660 - DNA methylation indices of cancer risk factors - 24/11/2020

B number: 
B3660
Principal applicant name: 
Matthew Suderman | University of Bristol (United Kingdom)
Co-applicants: 
Scott Waterfield, Dr Paul Yousefi, Professor Caroline Relton
Title of project: 
DNA methylation indices of cancer risk factors
Proposal summary: 

Cancer outcomes are improved when it is detected early. There is therefore a need for assays for identifying individuals with high cancer risk that can be applied to peripheral tissues such as blood or saliva. There is strong evidence that DNA methylation levels in these tisues encodes biomarkers for cancer risk factors such as cigarette smoke exposure, BMI, diabetes and biological aging. We plan to create DNA methyhlation models of cancer risk factors that can be combined to identify individuals with high cancer risk using peripheral blood samples.

Impact of research: 
We hope to eventually develop non-invasive tests for prioritizing individuals from the general population with higher cancer risk for further cancer screening.
Date proposal received: 
Monday, 16 November, 2020
Date proposal approved: 
Tuesday, 24 November, 2020
Keywords: 
Epidemiology, Cancer, Computer simulations/modelling/algorithms, Microarrays, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics

B3662 - Does opting in or out affect the take up of incentives in a long running population-based cohort study A nested randomised tria - 24/11/2020

B number: 
B3662
Principal applicant name: 
Kate Northstone | University of Bristol, UK (United Kingdom)
Co-applicants: 
Dr Dan Smith
Title of project: 
Does opting in or out affect the take up of incentives in a long running population-based cohort study: A nested randomised tria
Proposal summary: 

Effective strategies are critical to engage and retain participants of long term studies. A recent systematic review identified that the most common retention strategy employed was a cash/voucher incentive (59/95 studies reviewed)1. The Avon Longitudinal Study of Parents and Children has been collecting data annually from participants for over 30 years. Participants (parents and their offspring now aged ~28) are offered a £10 high street shopping voucher to complete our annual questionnaires. Across those generations we would anticipate upwards of 10,000 completed questionnaires. This comes at a substantial financial burden of over £100,000. Anecdotally, we are aware that some participants do not use their voucher once claimed or would be happy to complete regardless. The study has always provided an opt-out option for participants to indicate that they do not wish to receive their voucher, however, we were interested to see whether an opt-in option could introduce cost saving. We therefore randomised participants receiving invitations to complete the last annual questionnaire (late 2019/early 2020) to opt-out of receiving their voucher or to opt-in.

Impact of research: 
Date proposal received: 
Friday, 20 November, 2020
Date proposal approved: 
Tuesday, 24 November, 2020
Keywords: 
Epidemiology, cohort study management

B3663 - Depressive symptoms from childhood to adulthood - 24/11/2020

B number: 
B3663
Principal applicant name: 
Tamsin Jane Ford | University of Cambridge (United Kingdom)
Co-applicants: 
Mr Pascal Schlecter, Dr Sharon Neufield, Professor Paul Wilkinson
Title of project: 
Depressive symptoms from childhood to adulthood
Proposal summary: 

DDepression affects up to 300 million people worldwide and is one of the greatest causes of disability in the world. While many aspects of depression trajectories from adolescence to adulthood are well understood, depression is still among the most unreliable diagnoses of all categorical mental disorders. Additionally, changes in symptom levels across adolescence and young adulthood are as yet poorly understood. This may result from nosological conceptualizations of mental disorders that do not vary for children as compared to adolescents or adults. Only the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders describes irritability rather than depressed mood as an additional core symptom for children and adolescents. In this vein, researchers and practitioners often apply sum score models that reflect these considerations. However, these models rely on strong assumptions and we therefore aim to use Avon Longitudinal Study of Parents and Children data to investigate depressive symptoms in more depth.

Impact of research: 
This research will provide new insights into the course of depressive symptoms during adolescenc, providing useful information for both clinical research and practice about how the reporting of symptoms and their developments change, or not, over time. Specifically, these analyses will inform whether nosological conceptualizations of depression in children and adolescents are empirically justified. We will also probe the importance of parent-child discrepancies in reporting of depressive symptoms in predicting later outcomes. This may elucidate a new marker for sequelae following adolescent depression.
Date proposal received: 
Monday, 23 November, 2020
Date proposal approved: 
Tuesday, 24 November, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Computer simulations/modelling/algorithms, Development

B3659 - Effects of adolescent physical activity on physical and mental health in adulthood novel multivariate pattern analysis approach - 18/11/2020

B number: 
B3659
Principal applicant name: 
Ahmed Elhakeem | MRC IEU
Co-applicants: 
Dr Matteo Sattler
Title of project: 
Effects of adolescent physical activity on physical and mental health in adulthood: novel multivariate pattern analysis approach
Proposal summary: 

The benefits of physical activity (PA) for health are well established. However, limited evidence is available on the relative importance of specific intensities of PA as well as sedentary time for major health outcomes. In conventional analyses, accelerometer data are collapsed into only a few intensities (e.g. light, moderate-to-vigorous).This causes substantial loss of information and limits the detection of the relative importance of specific intensities. In this project we will use a novel multivariate pattern analysis approach to describe the entire PA intensity spectrum and examine the relative importance of different PA intensities on physical and mental health and mental wellbeing.

Impact of research: 
By using multivariate pattern analysis to study the the entire PA intensity spectrum and how this related to major health measures in adulthood, this study will advance our understanding how different intensities fo activity in adolescence relate to adult health.
Date proposal received: 
Friday, 13 November, 2020
Date proposal approved: 
Wednesday, 18 November, 2020
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Blood pressure, BMI, Bones (and joints), Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Metabolic - metabolism, Physical - activity, fitness, function, Statistical methods

B3652 - Genetics Adverse Childhood Experiences ACEs and Developmental and Behavioral Outcomes - 18/11/2020

B number: 
B3652
Principal applicant name: 
Hexuan Liu | University of Cincinnati (United States)
Co-applicants: 
Dr. J.C. Barnes, Dr. Joseph Nedelec, Breanna Clark
Title of project: 
Genetics, Adverse Childhood Experiences (ACEs), and Developmental and Behavioral Outcomes
Proposal summary: 

While previous research has consistently shown a relationship between adverse childhood experiences (ACEs) and developmental and behavioral outcomes later in life, understanding of mechanisms that explain the relationship is still insufficient. In particular, the role of genetics remains unknown. In this project, we propose to study how genetic factors and ACEs jointly and interactively affect individuals' developmental and behavioral outcomes, such as delinquent behavior and substance use. Specifically, we propose to examine whether and to what extent the influence of ACEs on the developmental and behavioral outcomes depends on children’s genetic susceptibility. Moreover, to what extent effects of parental genetic risk on child’s developmental and behavioral outcomes operate via ACEs.

Impact of research: 
The impact of this research will be three-folded. First, it improves our understanding of the role of genetics in research of ACEs on children’s developmental and behavioral outcomes. Second, it highlights the importance of childhood environment on children’s developmental trajectory. Finally, it provides insights to studies of intergenerational influences.
Date proposal received: 
Friday, 13 November, 2020
Date proposal approved: 
Wednesday, 18 November, 2020
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., GWAS, Childhood - childcare, childhood adversity, Development, Genomics, Genome wide association study, Offspring, Parenting

B3657 - GWAS of age of peak velocity of depressive symptoms and investigation of associated variables - 24/11/2020

B number: 
B3657
Principal applicant name: 
Kate Tilling | University of Bristol
Co-applicants: 
Miss Amy Campbell, Dr Alex Kwong, Dr Robyn Wootton, Dr Nicole Warrington, Dr Ahmed Elkaheem
Title of project: 
GWAS of age of peak velocity of depressive symptoms and investigation of associated variables
Proposal summary: 
Impact of research: 
Improved understanding of the genetic underpinnings of the development and progression of depression, which can then improve the identification of intervention targets and individuals for whom interventions would be relevant.
Date proposal received: 
Thursday, 12 November, 2020
Date proposal approved: 
Wednesday, 18 November, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Statistical methods, Sex differences

B3642 - Metabolic Health and Obesity-Relevant Diseases - 13/11/2020

B number: 
B3642
Principal applicant name: 
Marc J. Gunter | International Agency for Research on Cancer (IARC) (France)
Co-applicants: 
Dr Mary Playdon
Title of project: 
Metabolic Health and Obesity-Relevant Diseases
Proposal summary: 

Metabolic health is emerging as an important risk and prognostic factor for metabolic diseases, including cardiovascular disease (CVD), diabetes and cancer. (1-12) Metabolic health has been defined according to the presence or absence of a minimum number of cardiometabolic risk factors defined according to clinical cut-points (i.e. elevated waist circumference, triglycerides, blood pressure, and fasting glucose, low HDL-cholesterol, insulin resistance (HOMA-IR) and inflammatory biomarkers (hsCRP), or pharmacological treatment for these parameters). Obesity is associated with poor metabolic health, but metabolically unhealthy individuals may be at high risk of metabolic diseases, independent of BMI (metabolically unhealthy normal-weight phenotype, MUHNW) and obese individuals that are metabolically healthy may have similar disease risk to their lean counterparts (metabolically healthy obese phenotype, MHO). (1) Analysis of data from the US National Health and Nutrition Examination Survey showed that a substantial proportion of overweight or obese individuals are metabolically healthy and over 30% of normal weight individuals are cardiometabolically unhealthy. (13) The etiologies of the associations between these phenotypes and cardiometabolic disease risk are unclear. Recent studies have demonstrated the utility of using a metabolomics approach to explore the concepts of MUHNW and MHO in relation to cardiometabolic disease endpoints. For example, an 'obese metabolome' (metabolites related to insulin resistance, branched chain and aromatic amino acids, nucleotide metabolites, and several lipid classes) associated with a 2 to 5-fold increased risk of cardiovascular events, independent of BMI, in the TwinsUK cohort. (14) Matched for BMI, MUHNW individuals had higher visceral adiposity, higher blood pressure and were also more likely to become obese over time compared with their metabolically healthy lean counterparts. Such findings point towards the potential of metabolomics for disease risk stratification, where BMI alone can fail to identify a significant proportion of individuals that may be at risk for cardiometabolic disease. We propose to leverage the unique resources of COMETS to determine metabolites associated with metabolic health, how this profile associates with obesity-relevant diseases (i.e. obesity-related cancers and cardiovascular disease), and the extent to which metabolites mediate the association of body mass index with these outcomes.

Impact of research: 
We propose to leverage the unique resources of COMETS to determine metabolites associated with metabolic health, how this profile associates with obesity-relevant diseases (i.e. obesity-related cancers and cardiovascular disease), and the extent to which metabolites mediate the association of body mass index with these outcomes.
Date proposal received: 
Thursday, 5 November, 2020
Date proposal approved: 
Friday, 13 November, 2020
Keywords: 
Epidemiology, Diabetes, Obesity, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Metabolic - metabolism

B3653 - Birth mode impact on social behavior - 13/11/2020

B number: 
B3653
Principal applicant name: 
Will Kenkel | University of Delaware (USA)
Co-applicants: 
Title of project: 
Birth mode impact on social behavior
Proposal summary: 

This research will investigate whether birth mode shapes social behavior in childhood and adolescence. Cesarean delivery results in the newborn being exposed to lower levels of several important hormones than newborns delivered vaginally. These same hormones are known to shape social behavior throughout development, which leads us to hypothesize that birth is an important time for the developing brain. Disrupting hormonal signaling at birth via cesarean delivery is thus likely to impact the newborn's development.

Levels of each of the ‘birth signaling hormones’: oxytocin, arginine vasopressin, epinephrine, norepinephrine, and the glucocorticoids are lower following delivery by cesarean section compared to vaginal delivery, and there is substantial evidence for each of these hormones that manipulations in early life results in long-term neurodevelopmental consequences. This set of hormones has been extensively studied for their various roles in regulating social behavior in humans and non-human animals, often in a developmental context such as this, where manipulating their levels in early life alters social behavior throughout the rest of development. Furthermore, epidemiological associations have linked cesarean delivery with increased risk of autism spectrum disorder diagnosis and delayed social skills in early childhood. Finally, premature delivery is associated with markedly diminished rates of romantic attachment and sexual behavior. Thus, through multiple lines of evidence, we arrive at the central hypothesis: that birth mode can shape social behavior throughout the rest of life.

Impact of research: 
I hope that this work will yield a richer understanding of the neurodevelopmental consequences of birth mode. The next step for my research will be to experimentally explore these questions in a rodent model.
Date proposal received: 
Friday, 6 November, 2020
Date proposal approved: 
Friday, 13 November, 2020
Keywords: 
Endocrinology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Childhood - childcare, childhood adversity, Development, Equipment - MRI, Mothers - maternal age, menopause, obstetrics, Puberty

B3654 - Adolescent anxiety and depressive symptoms and subsequent intimate partner violence the impact of mental health support - 30/11/2020

B number: 
B3654
Principal applicant name: 
Annie Herbert | University of Bristol (United Kingdom)
Co-applicants: 
Dr. Abigail Fraser, Dr. Jon Heron, Prof. Gene Feder, Dr. Christine Barter, Rosie Cornish
Title of project: 
Adolescent anxiety and depressive symptoms and subsequent intimate partner violence: the impact of mental health support
Proposal summary: 

Around one-third of young people in the UK have suffered intimate partner violence (emotional, physical, or sexual abuse from a romantic partner) by the time they turn 21. This is more likely for those who have had symptoms of anxiety or depression during their teenage years. A common form of support for anxiety or depression at this age is through the GP - who might offer either psychological therapy (like counselling sessions, or cognitive behavioural therapy), or drug treatment (such as anti-depressants), to try to reduce anxiety and depression symptoms. This might also reduce likelihood of intimate partner violence later on, but there so far this has not been studied.

Impact of research: 
Recent qualitative interviews with young survivors of IPVA, aged 18-25, found that the large majority had experienced mental health problems such as anxiety or depressive symptoms since adolescence, and though almost all received some form of referral, they also perceived access to or the form of support as either insufficient or inconsistent. Findings should go some way to addressing the uncertainty around mechanisms and the potential impact of mental health and other services on service users. These findings will be of interest to academics and public health practitioners in the fields of mental health and domestic violence.
Date proposal received: 
Sunday, 8 November, 2020
Date proposal approved: 
Monday, 9 November, 2020
Keywords: 
Epidemiology, Mental health, Intimate Partner Violence, Statistical methods, Intimate Partner Violence, Anxiety, Depression, Treatment, Electronic Health Records, Primary Care

B3650 - LATERALCOG - Typical and atypical development of laterality - 09/11/2020

B number: 
B3650
Principal applicant name: 
SEGOND Hervé | Université de Strasbourg (FRANCE)
Co-applicants: 
HAMAOUI Jad
Title of project: 
LATERALCOG - Typical and atypical development of laterality
Proposal summary: 

The scientific literature provides several elements in favor of the existence of a link 1. between the fetal position at the end of gestation and the development of laterality, on the one hand; 2.between the type of fetal positioning (cephalic vs. breech) and developmental disorders of laterality and interhemispheric communications involved in cognitive functioning, on the other hand (cf. for review Güntürkün, & Ocklenburg, 2017 ). However, a lack of consensus remains today as to the nature of the relationship between the lateralization degree and cognitive development. Some theoretical positions consider that cognitive deficits are noted in individuals whose laterality is weakly established, in other words ambidextrous, while others consider ambilaterality as an advantage both in terms of language and visuospatial abilities (Boles & Barth , 2011; Chiarello, Welcome, Halderman, & Leonard, 2009; Johnston, Nicholls, Shah, & Shields, 2009). Innovatively, we suggest that this lack of consensus could be attributed to the existence of two distinct causes of ambidexterity with different developmental consequences.

Impact of research: 
The development of knowledge in this field constitutes a major societal issue, given the evocation in the scientific literature of the frequent belonging of "laterality disorders" to the clinical picture of many developmental and learning disorders in children (Kershner, 2019; Penolazzi, Spironelli, Vio & Angrilli, 2006; Xu, 2014), disorders that are most often diagnosed too late, during the first school learning, without allowing us to have a precise perception of the nature of these laterality disorders. This issue is all the more important given that these laterality disorders affect a large part of the population in vulnerable situations, since they are not only associated with disturbances in oral and written language (including developmental dyslexia, to which we are concerned, which concerns 6 to 15% of school-age children, dysgraphia, dysorthography, dysphasia and language delay), but also intellectual deficit, psychoses (e.g. schizophrenia), neuro-developmental disorders such as autism (affecting 1 in 150 people in France, according to the High Autority of Health, 2017), epilepsy, as well as deviant behavior. These laterality disorders could even appear as an interesting way of research in the determination of the etiological factors of the Coordination Acquisition Disorders (CAD) or Developmental Coordination Disorders (DCD), also called developmental dyspraxia (Gérard and al., 2005), resulting in early impairment of postural control (static and dynamic balance disorders), coordination and motor learning (lack of tonic regulation, slowness, imprecision, difficulties in relation with novelty, writing impairment), whose co-occurrence with specific language and reading disorders is noted in ± 60% of DCD cases (Vaivre-Douret et al., 2011). The investigation of the links between laterality in development and dyslexia is also part of the incentives of the various calls for scientific projects aimed at understanding the mechanisms at play in the late expression of lasting disorders (such as dyslexia constellation). In addition, the developmental consequences of breech birth would provide a very important source of information for our partners in obstetric hospital services, with a view to guide the evolution of childbirth practices (births by caesarean section vs. routes natural).
Date proposal received: 
Thursday, 5 November, 2020
Date proposal approved: 
Monday, 9 November, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, - Developmental disorders - autism - Cognitive impairment - Learning difficulty e.g. dyslexia - Pregnancy - e.g. postnatal depression, birth outcomes... - Speech/language problem - Coordination Development Disorder , - Qualitative study -Statistical methods, - Birth outcomes - e.g. state of the neonate, presentation during pregnancy, presentation at onset of labor and at delivery - Method of delivery - Cognition - cognitive function - Development - Handedness - Intelligence - memory - Mothers - maternal age, obstetrics - Siblings - Speech and language - Balance - Laterality

B3651 - Microbiome transfer and intergenerational transmission of mental health - 09/11/2020

B number: 
B3651
Principal applicant name: 
Sam Cartwright-Hatton | university of sussex (United Kingdom)
Co-applicants: 
Abigail Thomson, Dr Kathryn Lester
Title of project: 
Microbiome transfer and intergenerational transmission of mental health
Proposal summary: 

Mental health problems run in families. This arises from a range of genetic and environmental factors.

Recently, we have seen the impact that the human microbiome has on physical health (e.g inflammatory bowel disease, asthma, obesity) and mental health (depression, anxiety, autism).

Like mental health, the microbiome also runs in families, likely because of environmental transfer of microbiota between family members and, in particular, the seeding of the neonatal microbiome during the birth process. We wondered whether the sharing of microbiomes within families may partially explain familial similarities in mental health.

It is not possible to conduct an experiment, interrupting the transfer of microbiota from mother to child, to see if this had an impact on transfer of intergenerational risk for mental health problems. However, nature (helped along by NHS maternity services) provides us with a natural experiment: Approximately 20-25% of births are via caesarean section, and there is mounting evidence that this results in substantially lower mother-child microbiome transfer than vaginal birth. This microbiome transfer process can be further interrupted by other factors, including prenatal/perinatal antibiotic use and breastfeeding practices.

This study will explore the impact of early-life microbiome transfer on the intergenerational transmission of mental health problems.

Impact of research: 
To our knowledge, this research will be the first to offer an insight into the mental health impacts of disrupted microbiome colonisation at birth. More particularly, it will allow us to explore the role of the intergenerational transmission of microbiome on the intergenerational transmission of mental health - a potential new mechanism through which risk factors for child mental health are forged.
Date proposal received: 
Friday, 6 November, 2020
Date proposal approved: 
Monday, 9 November, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Microbiome

B3647 - Air pollution exposure and childhood obesity - 02/11/2020

B number: 
B3647
Principal applicant name: 
Serena Fossati | ISGLOBAL (Spain)
Co-applicants: 
Martine Vrijheid
Title of project: 
Air pollution exposure and childhood obesity
Proposal summary: 

Prenatal exposure to air pollution is robustly associated with fetal growth
restriction and low birth weight, a risk factor for altered cardio-metabolic diseases
later in life. Air pollution has also been associated with obesity and
cardiometabolic disease in adulthood. However, little is known on the association
between air pollution and obesity in infancy and childhood

Impact of research: 
Date proposal received: 
Friday, 30 October, 2020
Date proposal approved: 
Monday, 2 November, 2020
Keywords: 
Epidemiology, Obesity, Statistical methods, Environment - enviromental exposure, pollution

B3625 - Green Spaces and Multiple Child Health Outcomes - 02/11/2020

B number: 
B3625
Principal applicant name: 
Amanda Fernandes | ISGLOBAL (Spain)
Co-applicants: 
Serena Fossati, Mark Nieuwenhuijsen, Martine Vrijheid
Title of project: 
Green Spaces and Multiple Child Health Outcomes
Proposal summary: 

Early-life urban stressors have been identified as a risk to the onset of non-communicable diseases. An accumulating body of evidence is suggestive for health-promoting effects of exposure to green spaces. However, the association between green spaces and harmful or beneficial effects on children health is still poor for most outcomes, and the underlying mechanisms remain unclear. Outcome wide analysis have recently been proposed as a way to evaluate the effects of exposures over numerous important outcomes. Indeed, some exposures may be harmful for some outcomes and beneficial for others, including green spaces exposures. This approach also has the advantage to better control for confounding for the effects of the exposure on all outcomes simultaneously. It is different from the traditional one-outcome approach and more similar to GWAS (genome wide associations) or EWAS (epigenome wide associations) or ExWAS (exposome wide associations). For outcome-wide approaches, larger datasets are needed so LifeCycle is a good opportunity to apply this novel method. The idea is to add as many outcomes as possible, this is the great interest of the outcome wide approach.

Impact of research: 
Date proposal received: 
Friday, 30 October, 2020
Date proposal approved: 
Monday, 2 November, 2020
Keywords: 
Epidemiology, Allergy, Cognitive impairment, Obesity, Statistical methods, Childhood - childcare, childhood adversity

B3648 - Exposure to urban natural environments and birth outcomes - 02/11/2020

B number: 
B3648
Principal applicant name: 
Maria Torres | ISGLOBAL (Spain)
Co-applicants: 
Martine Vrijheid
Title of project: 
Exposure to urban natural environments and birth outcomes
Proposal summary: 

Previous studies have associated exposure to urban natural environments during
pregnancy with improved birth outcomes. But there are still some gaps in the
knowledge:
(1) The results showed different patterns in different settings maybe because of
their differences in climate, vegetation type, culture, etc. There is a need to
evaluate this association in a larger sample size with standardized methodology
from several cohorts
(2) The majority of previous studies are focused on birth weight. But the available
evidence on the association between natural environments and other birth
outcomes is still scarce or null
(3) The vast majority of previous studies are focused on green spaces and the
availability of studies focused on the association between blue spaces and birth
outcomes is very scarce

Impact of research: 
Date proposal received: 
Friday, 30 October, 2020
Date proposal approved: 
Monday, 2 November, 2020
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes

B3644 - Infection during childhood and cognitive function - 09/11/2020

B number: 
B3644
Principal applicant name: 
Emma Anderson | University of Bristol
Co-applicants: 
Dr Evie Stergiakouli , Rebecca Scanlan
Title of project: 
Infection during childhood and cognitive function
Proposal summary: 
Impact of research: 
Improve scientific understanding of the impact of childhood infections on cognitive capability of children, and thus improving our understanding of whether infection in childhood could go on to affect risk of Alzheimer's disease by lowering cognitive function. May help inform public health prevention strategies for dementia
Date proposal received: 
Wednesday, 28 October, 2020
Date proposal approved: 
Monday, 2 November, 2020
Keywords: 
Epidemiology, Cognitive impairment, Infection, Statistical methods, Cognition - cognitive function

B3646 - Computational approaches to modelling parent -infant behavioural data - 11/11/2020

B number: 
B3646
Principal applicant name: 
Rebecca Pearson | Bristol Medical School
Co-applicants: 
Romana Burgess, Professor Ian Nabney, Ilaria Costantini, Dr Iryna Culpin
Title of project: 
Computational approaches to modelling parent -infant behavioural data
Proposal summary: 

This PhD project will use data modelling techniques to explore the behavioural transmission of mental health conditions from mother to infant. This will involve an extensive analysis of coded video data of mother-infant interactions captured using wearable headcams in CoCo90s and comparing to other data in partner cohorts. Initial data analysis will involve computing the frequencies, durations, and rates per minute of behaviours for each subject. Following this, statistically significant inferences between modes will be extracted using graphical modelling, Bayesian inference and pattern recognition methodologies. Additionally, behavioural comparisons will be drawn between mothers with and without mental health conditions. It is hoped that findings from this research will be used to inform interventions to improve mental health outcomes for mother and infant.

Impact of research: 
Methodological innovation and clinical insights
Date proposal received: 
Thursday, 29 October, 2020
Date proposal approved: 
Monday, 2 November, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Computer simulations/modelling/algorithms

B3645 - Is there a causal association between insulin signalling and myopia pathogenesis - 11/11/2020

B number: 
B3645
Principal applicant name: 
Denize Atan | University of Bristol
Co-applicants: 
Mr Max Gillies
Title of project: 
Is there a causal association between insulin signalling and myopia pathogenesis?
Proposal summary: 

Myopia, or short-sightedness, is one of the most common causes of sight impairment worldwide. By 2050, five billion people- half the world’s population- will be short-sighted, compared to ~1.4 billion people today.
People with myopia have relatively long eyes, so that light is focused in front of the retina instead of directly onto it. Since the eye continues to grow throughout childhood, someone who develops myopia as a child will continue to get worse as they grow older, with greater risk of sight-threatening complications.
Previously, we showed that for each additional year we spend in education, the more myopic we become, on average, as a population. Evidence from other studies suggests that this may be because we spend less time outside, reducing our exposure to natural daylight. Other risk factors for myopia include the time we spend on near work, urbanization, socioeconomic position, diet, pregnancy-related factors and genetics. Children with myopia tend to engage in less physical activity, but physical activity alone is not protective against myopia.
Myopia is more prevalent in countries adopting a Western diet and lifestyle, and many of the genes that increase the risk of myopia are involved in insulin/glucose signalling and obesity/fat metabolism. Insulin signalling also appears to influence the normal growth of the eye. As the Western diet is linked to greater intake of food with higher energy loads, one hypothesis is that compensatory increases in blood glucose and insulin levels send increased growth signals to the eyes.
This project aims to determine how genetic and environmental factors interact with insulin signalling to affect myopia. Changes in insulin signalling happen naturally in children around puberty, and so we would like to use information in the Avon Longitudinal Study of Parents and Children on eye growth, glasses prescriptions, blood levels of glucose and insulin before, during and after puberty on thousands of children followed prospectively from birth, to find out how they interact to affect eye growth. Additionally, there are normal variants in our genes that influence fasting levels of insulin and glucose and we will find out how these genetic variants are linked to myopia. These analyses should provide novel insights into the relationship between insulin signalling and myopia, and have the potential to identify novel targets for treatment.

Impact of research: 
The above analyses will help us determine whether genetic and environmental changes in insulin/IGF1 signalling are major determinants of axial growth in children and myopia pathogenesis. If so, they would explain how myopia is linked to increasing urbanisation, diet, BMI, height and PHV during puberty, and why GWAS and studies of animal models of myopia implicate insulin/IGF pathways. They might also point the way to novel therapies for myopia that target downstream effector molecules in the insulin/IGF1 signalling pathway, e.g. PI3K/AKT. The efficacy of topical atropine eye drops for myopia suggests that local or topical delivery routes could be an option
Date proposal received: 
Wednesday, 28 October, 2020
Date proposal approved: 
Friday, 30 October, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Diabetes, GWAS, Statistical methods, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Nutrition - breast feeding, diet, Puberty, Statistical methods, Vision, BMI, Childhood - childcare, childhood adversity, Epigenetics, Genetic epidemiology, Genetics, Genome wide association study, Hormones - cortisol, IGF, thyroid, Mendelian randomisation

B3639 - Cell type-specific DNA methylation meta-analysis for ADHD symptoms - 27/10/2020

B number: 
B3639
Principal applicant name: 
Dr Doretta Caramaschi | MRC IEU
Co-applicants: 
Mandy Meijer, MSc, Dr Marieke Klein, PhD
Title of project: 
Cell type-specific DNA methylation meta-analysis for ADHD symptoms
Proposal summary: 

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, characterized by symptoms of inattention and/or hyperactivity and impulsivity. Not only people with ADHD experience these symptoms, but also people without ADHD can show these symptoms. The development of ADHD (symptoms) is partially genetic, and can also be influenced by factors in someone’s surrounding, for example prenatal nicotine exposure. Genetics and surrounding factors can interplay and this can be reflected in DNA methylation. Knowing which DNA methylation patterns are associated with ADHD symptoms, can teach us more about the molecular mechanisms underlying ADHD (symptoms). These DNA methylation profiles are cell type-specific. Up to now, most methylome-wide association studies have been performed in whole blood, in which multiple blood cells are present. Because the different blood cells have distinct DNA methylation profiles, it is possible that meaningful signal is cancelled out in whole blood measures. Therefore, we think there might be valuable signal in cell type-specific DNA methylation, done by a statistical method called epigenomic deconvolution. This could give us more insight in the molecular mechanisms of ADHD symptoms.

Impact of research: 
We hope to find robust and specific DNA methylation associations to ADHD symptoms, in the different domains in a cell type-specific manner. This information could lead to the identification of new biomarkers and potential new biological pathways to better understand ADHD-related behaviour.
Date proposal received: 
Tuesday, 20 October, 2020
Date proposal approved: 
Tuesday, 27 October, 2020
Keywords: 
Epidemiology

B3640 - Investigating genetic influences on ASD autistic traits and trajectories of autistic traits - 27/10/2020

B number: 
B3640
Principal applicant name: 
Zoe Reed | University of Bristol (UK)
Co-applicants: 
Professor Marcus Munafò, Professor Geoge Davey Smith
Title of project: 
Investigating genetic influences on ASD, autistic traits and trajectories of autistic traits
Proposal summary: 

Previous research has shown that autism spectrum disorder is caused by a combination of both genetic and environmental factors. Although studies have identified genes that associated with having ASD, the specific pathways involved in the development and progression of ASD is not well understood. In addition, less is known about the genetic contributions to autistic traits in the more general population and also on the progression of these autistic traits. In this project we would like to address this important gap in our knowledge by investigating these genetic contributions in more detail and by attempting to identify the specific biological pathways that lead to the development of ASD, autistic traits and the progression of these traits over time. To do this we will use data from several cohorts, including Children of the Nineties. The results from this study may inform population health and may help develop more targeted interventions for individuals with ASD symptoms.

Impact of research: 
This research will lead to a better understanding of the genetic influences on autistic trait trajectories which will be useful to compare to those for ASD and autistic traits. Results from our analyses may inform future population health policies and interventions targeted at those with symptoms of ASD.
Date proposal received: 
Friday, 23 October, 2020
Date proposal approved: 
Tuesday, 27 October, 2020
Keywords: 
Epidemiology, Developmental disorders - autism, GWAS, Statistical methods, Genetic epidemiology, Genetics, Genome wide association study, Mendelian randomisation, Statistical methods

Pages