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.

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B3005 - Hypertensive disorders of pregnancy and mental and behavioural disorders in offspring - 22/03/2018

B number: 
B3005
Principal applicant name: 
Rosa Alati | University of Queensland (Australia)
Co-applicants: 
Berihun Dachew, Ass. Prof Abdullah A Mamun, Dr. Kim Betts
Title of project: 
Hypertensive disorders of pregnancy and mental and behavioural disorders in offspring
Proposal summary: 

There has been increasing research attention to the impact of in utero exposures to specific perinatal risk factors and their potential impact on diseases later in life. One of these is hypertensive disorders of pregnancy (HDP), a perinatal condition which affects up to 10% of pregnancies globally. Current evidence shows that HDP are associated with an increased risk of offspring cardiovascular, immune, metabolic disorders in later life. HDP are also responsible for various adverse perinatal outcomes such as preterm birth, low birth weight and intrauterine growth restriction, which are known risk factors for numerous mental health morbidities. In addition, HDP may also affect brain development via utero-placental vascular insufficiency and fetal malnutrition and lead to subsequent neurobehavioral difficulties. A lot of research has been conducted on the associations between HDP and cognitive functioning in offspring, however, evidence on the effect of intrauterine exposure to HDP on offspring mental and behavioural disorders is not well-established.
Two systematic reviews conducted by this team, one currently under review and the other one accepted by the British Journal of Psychiatry have shown that HDP had a negative impact for a range mental or behavioural disorders. Our finding showed that preeclampsia was associated with increased risk of offspring schizophrenia. The risk of Autism spectrum disorder was also 32% higher in offspring who had intrauterine exposure to preeclampsia as compared to those non-exposed. However, we found inconclusive finding on the effect of HDP and other mental and behavioural disorders, suggesting the need of further studies to progress this area of research. Following on from these findings, this PhD project aims to add to the existing evidence in a meaningful way by conducting a high quality, large sample, birth cohort study.

Impact of research: 
This research has a potential to provide accurate information on whether there is a direct link between HDP and a range of mental and behavioural disorders in offspring. This will have potential benefits in terms of advancing the existing knowledge and help clinical decision making for interventions during pregnancy, thereby improving near and long term offspring mental health outcomes.
Date proposal received: 
Wednesday, 29 November, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Epidemiology, Hypertensive disorders of pregnancy, preeclampsia, gestational hypertension, mental disorders, behavioural disorders, offspring

B3095 - Genome-wide association analysis of voting behaviour for Mendelian randomization - 11/04/2018

B number: 
B3095
Principal applicant name: 
Neil Davies | MRC IEU
Co-applicants: 
Nic Timpson, Charlie Hatcher
Title of project: 
Genome-wide association analysis of voting behaviour for Mendelian randomization
Proposal summary: 

Genome-wide association studies (GWAS) have been critical in identifying thousands of genetic variants associated with complex traits and diseases. For certain complex traits however, it may be the case that there is difficulty in phenotypic measurement and this can lead to issues of statistical power. This is particularly problematic for behavioural phenotypes that may be predominantly determined by the environment, as is the case for educational attainment and well-being (Okbay et al., 2016; Okbay et al., 2016; Rietveld et al., 2013). Genetic analyses of such phenotypes can be hindered by the fact that individual SNPs have limited explanatory power and any associations found may not be causal or may be mediated by many other intermediate phenotypes (Krapohl et al., 2014). However, such studies have enabled the description of common genetic contributions to complex behaviours. Taken together, these GWAS results form a pool of genetic variants which may then be used in Mendelian randomization (MR) analyses; both looking at the effect of these features on outcomes but also the effect of outcomes on them.

This project will use newly collected data in the Avon Longitudinal Study of Parents and Children cohort to analyse voting behaviour. Firstly, we aim to conduct a GWAS on voting behaviour to discover any genetic variants associated with this complex trait. Additionally, we plan on considering the potential of using MR analysis to look at this behavioural phenotype. Specifically, we aim look at the effect of well instrumented risk factors on voting behaviour itself, i.e. ‘backwards MR’.

References
Krapohl, E. et al. The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence. Proc. Natl Acad. Sci. USA 111, 15273–15278 (2014).

Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses (vol 48, pg 624, 2016). Nature Genetics 48, 1591-1591 (2016).

Okbay, A. et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533, 539-+ (2016).

Rietveld, C.A. et al. GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment. Science 340, 1467-1471 (2013).

Impact of research: 
Date proposal received: 
Wednesday, 4 April, 2018
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B3114 - Tracking Sleep Phenotypes 2 15-05-2018 - 234902 - 26/05/2018

B number: 
B3114
Principal applicant name: 
Helen Heussler | Center for CHildren's Health Research. University of Qld (Australia)
Co-applicants: 
Emily Sawyer, Prof Karen Thorpe, Simon Smith , Ronny Gunnarson, Mamun Abdullah, Enda Byrne, Adam Ewing, Peter Blair
Title of project: 
Tracking Sleep Phenotypes (2) (15-05-2018 - 23:49:02)
Proposal summary: 

Sleep matters to those who care for young children. The duration and timing of sleep can have a profound effect on a young child’s everyday behaviour, learning and health and also has a significant impact on the routines and wellbeing of the adults who provide his or her care. Yet there is surprisingly little evidence regarding the developmental function of early sleep patterns. Current understanding of the processes underpinning normative transition in sleep patterns, the prevalence of specific sleep phenotypes and persistence in sleep patterns across time is limited. This study will utilise genetic and environmental data, alongside longitudinal sleep data to examine the prevalence, persistence and developmental significance of childhood sleep phenotypes.

This knowledge will inform clinical, public health and educational policy and practice where management of sleep is an issue of controversy and also inform parenting practice where early child sleep behaviours can have a major impact on family functioning, parent well-being and child development.

Impact of research: 
The focus of our research will be important in informing care practices particularly in early childhood settings and family contexts. Internationally the importance of sleep in long term health is growing but the available evidence and subsequent evidence for policy and practice is limited. In Australia and the US for example while there are significant recommendations for exercise and nutrition in young children the existing sleep recommendations are limited to sleep safety in the first year. (We are pleased to have Prof Peter Blair on the Team) Longitudinally the existence of tight phenotypes has been challenging to establish however using this data we hope to establish some genotype- phenotype relationships to help inform practice.
Date proposal received: 
Thursday, 17 May, 2018
Keywords: 
Clinical research/clinical practice, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Mental health, DNA sequencing, GWAS, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Epigenetics, Genomics, Intelligence - memory, Sleep

B602 - EU Call - ENRIECO

B number: 
B602
Principal applicant name: 
Prof Mark Nieuwenhuijsen (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
EU Call - ENRIECO
Proposal summary: 

We are writing to all the birth cohorts in Europethat we know have an interest in environment and health to ask them to participate in this coordinating action (list attached). We have already contacted quite a number of them and leaders in various projects such as GA2LEN, ESCAPE, HIWATE and they have agreed to participate. We would like you to read the text below and let us know if you are interested in taking part in this proposal. We need an answer very soon since the deadline for submission is 25 February. Besides extracting currently available information, we also hope to generate new information (but are limited to what can be done within a coordinating action and available funding) and we have proposed a number of ideas, but other ideas are welcome. Please indicate if you are interested in any asap (and correct any incorrect information), and whether you are willing to take the lead of any of the ideas/WPs.

Date proposal received: 
Thursday, 10 January, 2008
Keywords: 
Primary keyword: 

B3071 - Parental alcohol use and offspring mental health - 06/03/2018

B number: 
B3071
Principal applicant name: 
Marcus Munafò | MRC Integrative Epidemiology Unit (UK)
Co-applicants: 
Miss Kayleigh Easey, Dr Luisa Zuccolo, Professor Nicholas Timpson
Title of project: 
Parental alcohol use and offspring mental health
Proposal summary: 

Previous research has shown detrimental offspring outcomes for children prenatally exposed to alcohol. However, uncertainty remains as to whether these negative offspring outcomes are due to the intrauterine environment, or environmental influences after birth, for example parental lifetime drinking. Further investigation is required to assess the impact of parental alcohol use on offspring outcomes. The research that has been previously conducted in this area has focused on academic outcomes, with less focus on the influence maternal and partner drinking may have on offspring mental health.
In addition, valid reports of alcohol use may be affected by under-reporting. Using parental methylation markers that are predictive of alcohol use, could be a more biologically valid method for assessing alcohol consumption. These methylation-based biomarkers were developed by Liu et al (2018) and are currently being validated by co-applicants (LZ) in ALSPAC. The proposed study will use such biomarkers to assess if this produces a stronger signal, in comparison to self-reported alcohol use.

Impact of research: 
To further inform the evidence of child mental health risks and steps that can be taken to reduce harm.
Date proposal received: 
Tuesday, 20 February, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Mental health, alcohol

B3096 - Does cognitive vulnerability modify the association between stressful life events and future depression - 11/04/2018

B number: 
B3096
Principal applicant name: 
Marcus Munafò | University of Bristol (United Kingdom)
Co-applicants: 
Miss Sarah Peters, Professor Ian Penton-Voak
Title of project: 
Does cognitive vulnerability modify the association between stressful life events and future depression?
Proposal summary: 

Several studies have found that the experience of stressful life events (ranging from more severe events, such as divorce or bereavement, to daily hassles, such as family-related obligations) can lead to symptoms of depression. However, the impact of these events varies, and not everyone who experiences a stressful event goes on to experience depression. We’re interested in studying whether cognitive vulnerability, the tendency to make negative causal inferences about an event, can explain this difference (i.e., is an effect modifier). That is, the interpretation of the event, rather than exposure to the event alone, may be particularly important for predicting future depression. This study aims to investigate how the impact of stressful events varies between people, and why certain people go on to experience depression while others do not. These findings could inform potential targets for interventions which intend to prevent depressive symptoms.

Impact of research: 
Depression is a common, costly, and life-threatening illness. Understanding the impact of factors such as cognitive vulnerability on established risk factors for depression (such as stressful life events) is relevant to both etiologic models of depression and for the development and evaluation of more targeted interventions. Quick and accessible interventions that target cognitive vulnerability may be useful for treating depression and could be informed by this research.
Date proposal received: 
Monday, 9 April, 2018
Keywords: 
Epidemiology, Mental health, Statistical methods, Mental health, depression, stressful life events, cognitive vulnerability, cognitive styles

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