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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B989 - An item response theory analysis of the Childhood interview for DSM-IV Borderline Personality Disorders C1-BPD - 01/01/1900

B number: 
B989
Principal applicant name: 
Carla Sharp (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
An item response theory analysis of the Childhood interview for DSM-IV Borderline Personality Disorders (C1-BPD)
Proposal summary: 

We wish to investigate the measurement of borderline personality disorder (BPD) within the 11-12 year-old cohort of the ALSPAC data. Specifically, we intend to employ item response theory (IRT) methods on the BPD symptom criteria. IRT constitutes a latent trait approach to psychological measurement, modeling the probability of endorsing a given item (e.g., presence of affective instability) as a function of an individual's standing on the underlying construct (e.g., BPD).

The basic unit of IRT is the item characteristic curve (ICC), which depicts visually the relationship between the construct and a person's response to an item (Embretson & Reise, 2000). The shape of this curve is influenced by at least two parameters: difficulty and discrimination. The difficulty parameter represents the point at which the probability of endorsing an item is 50%. The discrimination parameter is the slope of the ICC at the value of the difficulty parameter. These parameters will provide important information for evaluating the performance of each BPD criterion, such as the level of BPD needed to meet the criterion and the degree to which it differentiates among higher and lower levels of BPD (Feske, Kirisci, Tarter, & Pilkonis, 2007).

Most applications of IRT require that the construct being measured is unidimensional. Several factor analytic investigations of the BPD criteria in adults have supported a unidimensional structure (Aggen, Neale, Roysamb, Reichborn-Kjennerud, & Kendler, 2009; Feske et al., 2007; Fossati, Maffei, Bagnato, Donati, Namia, & Novella, 1999), while others have reported a structure sufficiently unidimensional for IRT purposes (Johansen, Karterud, Pedersen, Gude, & Falkum, 2004; Sanislow et al., 2002), as evidenced by high factor intercorrelations (Embretson & Reise, 2000). To date, only one study (Becker, McGlashan, & Grilo, 2006) has conducted factor analysis of the BPD criteria in a youth sample, the results of which did not reveal a unidimensional structure. However, this study employed principle component analysis with orthogonal rotation and, thus, did not report the magnitude of factor intercorrelations. Taken together, these studies provide reason to believe that the BPD criteria may be sufficiently unidimensional to employ a traditional IRT-based model. However, in the event that the BPD criteria are not unidimensional in the ALSPAC data, multidimensional or categorical confirmatory factor analysis will be employed.

In order to investigate our aims, we will need the CI-BPD data that correspond to each of the 9 DSM-IV symptom criteria, including the questions used to inform judgment of whether the symptom was present.

Date proposal received: 
Monday, 19 April, 2010
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
ADHD, Behavioural Problems
Primary keyword: 

B698 - Study of CRHR1 and HSD11B1 genetic variants in ALSPAC - 01/01/1900

B number: 
B698
Principal applicant name: 
Santiago Rodriguez (Not used 0, Not used 0)
Co-applicants: 
Dr Tom Gaunt (Not used 0, Not used 0)
Title of project: 
Study of CRHR1 and HSD11B1 genetic variants in ALSPAC
Proposal summary: 
Date proposal received: 
Tuesday, 9 September, 2008
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Genetics
Primary keyword: 

B988 - Analysis of changes in fruit and vegetable intake as children get older in a UK cohort study - 01/01/1900

B number: 
B988
Principal applicant name: 
Miss Viviana Albani (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Analysis of changes in fruit and vegetable intake as children get older in a UK cohort study.
Proposal summary: 

Title: analyse the evolution of fruit and vegetable intake frequency of children from infancy to 15 years, segmenting by household socioeconomic status (SES) and parental attitudes.

Specific objective: the aim of the analysis is to explore trends in intake (amount and frequency) across children's ages in years to evaluate the possibility of tracking of food habits (specifically fruit and vegetable intake), and any trends in changes in intake along the child's lifecycle (e.g. frequency of intake tends to drop/rise at the age of X). The idea is to construct different series of average intake by socioeconomic groups, and by mothers' attitudes to fruits and vegetables and eating in general. The analysis of segmentation by socioeconomic group and attitudinal variables will be helpful not only in illustrating any difference in starting points in fruit and vegetable intake when children are categorised according to these variables, but also any persistence and/or broadening of inequality as children grow older.

Broader objective: secondary data analysis of trends in children's fruit and vegetable intake by socioeconomic grades and mothers' attitudes as part of the research agenda for a PhD project on Consumer Behaviour and Associated Change Drivers and Barriers in the Consumption of Fruits and Vegetables by Children.

Methods: graph plotting average and median intake (y axis) against age (x axis) for categories by SES (quintiles or tertiles of SES) and mothers' attitudinal characteristics. Statistical analyses (paired t tests and correlations) to test for tracking of food habits (Skinner et al. 2002).

Date proposal received: 
Friday, 16 April, 2010
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Diet, Eating Disorder
Primary keyword: 

B697 - A genome-wide association study of ankylosing spondylitis risk - 01/01/1900

B number: 
B697
Principal applicant name: 
Dr Dave Evans (Not used 0, Not used 0)
Co-applicants: 
Matt Brown (Not used 0, Not used 0), Prof John Reveille (Not used 0, Not used 0)
Title of project: 
A genome-wide association study of ankylosing spondylitis risk
Proposal summary: 

We have performed a large genome-wide association study in a few thousand ankylosing spondylitis patients and need to replicate several promising genetic associations. Although we have genotyped putatively associated SNPs in a new sample of cases, we need to obtain genotype data from a similarly sized european control sample on ~100 candidate SNPs. Since both cohorts have been genotyped on the Illumina 317K SNP chip, the ~1700 ALSPAC individuals for whom genome-wide SNP data is now available would be an obvious choice. Note that we are requesting a small number of candidate SNPs (i.e. ~100 SNPs) NOT the entire genome-wide dataset.

Date proposal received: 
Friday, 5 September, 2008
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Genetics
Primary keyword: 

B208 - Regulation of fasting glucose and birthweight the impact of variation in the glucokinase gene - 01/01/1900

B number: 
B208
Principal applicant name: 
Prof Tim Frayling (University of Exeter, UK)
Co-applicants: 
Title of project: 
Regulation of fasting glucose and birthweight: the impact of variation in the glucokinase gene.
Proposal summary: 

Variation in fasting glucose concentration (FPG) is important for human health. In the normal range FPG is associated with risk of type 2 diabetes and ischaemic heart disease independently of obesity. In pregnancy maternal FPG concentration is an important independent determinant of birth weight in non-diabetic mothers. There is evidence that the regulation of FPG has a strong genetic component.

The main regulator of FPG concentration is the enzyme glucokinase. Our preliminary data shows that common variants in the promoter region of the glucokinase gene are associated with FPG and fetal growth. The minor allele at GCK-30, present in 30% of the UK population raises FPG by0.06 mmol/l (0.04-0.11), p = 0.003; and, when present in the mother, birth weight by 64g (25-102), p = 0.001. We have next shown that variation, further upstream (rs3757840) of the gene, and with no obvious functional role, has a similar, but independent effect on FPG.

In this project we propose to test comprehensively the hypothesis that common genetic variation in GCK alters FPG and birth weight. We will use the latest approaches for capturing the important variation across a gene together with DNA resources from 28,799 mother-child pairs. This approach will establish, if our hypothesis is true, a definitive genetic component to the aetiology of normal variation in FPG and birth weight.

Date proposal received: 
Wednesday, 1 December, 2004
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Genetics, Obstetrics, Pregnancy, Birth weight
Primary keyword: 

B693 - Confirmation of Genome-Wide association findings for obesity and obesity related traits - 01/01/1900

B number: 
B693
Principal applicant name: 
Dr Ruth Loos (University of Cambridge, UK)
Co-applicants: 
Ken Ong (University of Cambridge, UK), Nick Wareham (University of Cambridge, UK)
Title of project: 
Confirmation of Genome-Wide association findings for obesity and obesity related traits
Proposal summary: 

Recent advances in high-throughput genotyping technologies, coupled with the development of massive databases such as the International HapMap Project that catalogues millions of SNPs (single nucleotide polymorphisms), have set the stage for genome-wide association studies. Genome-wide association (GWA) studies are designed as two- or three phased studies. The first phase requires a dense set of hundreds of thousands of SNPs across the human genome, genotyped in a large sample of well-characterised individuals. The second and third phases aim to replicate and fine-map the most significant findings of the first phase in other large cohorts. Eventually, genome-wide association studies will identify new gene variants, previously unanticipated, that will contribute to a better understanding of the etiology of common disease and complex traits.

Our GWA study is designed for the identification of new, unanticipated gene variants that contribute to variation in obesity as well as BMI, and related traits, including age at menarche. This GWA study is undertaken as a collaboration between the MRC Epidemiology Unit and the WT Sanger Institute (Dr Ines Barroso) using a case-cohort design. The 1713 cases (defined as those with a BMI greater than 30kg/m2) and a random control cohort of 2200 individuals have been selected from the EPIC-Norfolk prospective cohort study, a population-based cohort of 25.663 men and women aged 40-79 years recruited in Norfolk, UK between 1993 and 1997. All 3913 individuals have been genotyped for two dense SNP-chips; i.e. the 500K GeneChip Mapping Sets of Affymetrix and the Sentrix HumanHap300 BeadChip of Illumina. We are currently analysing associations of this genome-wide data with obesity as a dichotomous outcome in the case-cohort study and with BMI, age at menarche and various metabolic variables as quantitative traits within the cohort study.

In order to increase the power to detect true positive signals Phase 1 will be expanded by performing a meta-analysis of two other cohorts with similar GWA phenotypic and data. We have recently established a long term collaboration with Vincent Mooser (GSK) and colleagues, who have performed a GWA study in the GSK-Lausanne cohort. The GSK-Lausanne population is comparable to the EPIC data as it is a cohort study of 6,205 Europid men and women from Lausanne, aged 35-75 years. This collaboration has a general aim to identify genes that contribute to various metabolic traits. The summary statistics from these GWA studies on these traits will be shared and meta-analysed at the MRC Epidemiology Unit.

Key to genomewide association studies is replication of the initial findings in more populations with similar characteristics. New genes identified by GWA will be taken forward for rapid confirmation studies in several large cohort studies. In addition to ALSPAC, these include a second equal sized case-cohort study within the EPIC cohort (n=3,900), the MRC-Ely study (n = 1,700), the MRC-Fenland study (currently n = 2,000), the Hertfordshire study (n = Outline 3,000), and the European Youth Heart study (n = 2,700).

Date proposal received: 
Monday, 1 January, 1900
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Endocrine, Obesity, Weight
Primary keyword: 

B935 - Antioxidant gene modification of the effect of prenatal paracetamol on asthma - 01/01/1900

B number: 
B935
Principal applicant name: 
Prof Sief Shaheen (Imperial College London, UK)
Co-applicants: 
Prof John Henderson (University of Bristol, UK), Prof John Holloway (University of Southampton, UK), Dr Susan Ring (University of Bristol, UK)
Title of project: 
Antioxidant gene modification of the effect of prenatal paracetamol on asthma
Proposal summary: 

Having identified a possible interaction between a maternal Nrf2 SNP and prenatal paracetamol exposure on asthma risk, we would like to carry out further genotyping to confirm additional gene*paracetamol interactions.These include an additional Nrf2 SNP; GCL (relevant to glutathione synthesis); Melatonin receptor MTNR1b (melatonin is a powerful antioxidant linked to paracetamol toxicity); CYP2E1 (relevant to paracetamol toxicity).

Date proposal received: 
Friday, 18 December, 2009
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Allergies, Genetics, Respiratory, Atopy, Genes
Primary keyword: 

B415 - BLANK - 01/01/1900

B number: 
B415
Principal applicant name: 
(Not used 0, Not used 0)
Co-applicants: 
Title of project: 
BLANK
Proposal summary: 

Genetics, Speech and Language

Date proposal received: 
Thursday, 30 December, 1999
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Genetics, Speech & Language
Primary keyword: 

B2438 - Metabalomic profile of alcohol consumption in adolescents - 01/01/1900

B number: 
B2438
Principal applicant name: 
Tom Dudding (University of Bristol, UK)
Co-applicants: 
Nick Timpson (University of Bristol, UK), Dr Fotios Drenos (University of Bristol, UK), Prof Richard Martin (University of Bristol, UK)
Title of project: 
Metabalomic profile of alcohol consumption in adolescents
Proposal summary: 

Aims:

1) To assess the how alcohol consumption affects metabalomic profile

2) To identify a genetic instrument for metabolites that are associated with alcohol consumption

Date proposal received: 
Thursday, 7 May, 2015
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Alcohol
Primary keyword: 
Metabolomics

B929 - Bladder Control in Bilateral Cerebral Palsy a Population-based Study - 01/01/1900

B number: 
B929
Principal applicant name: 
Prof Gillian Baird (Guy's & St Thomas' Hospital, London, UK)
Co-applicants: 
Dr Anne Wright (The Portland Hospital for Women and Children, UK)
Title of project: 
Bladder Control in Bilateral Cerebral Palsy: a Population-based Study.
Proposal summary: 

With regards to children with cerebral palsy, very little information about attainment of urinary continence is available. The long-term physical, psychosocial and financial burden of incontinence in the cerebral palsy patient is considerable and in order for the paediatrician to begin addressing these important issues further information regarding the normal attainment of bladder control in children with cerebral palsy has to be established. This is the aim of this study.

METHODS

The original study:

The data in this study originate from a previously published population based study (Scrutton and Baird 1997) which established a cohort of children with bilateral cerebral palsy born from 1989 to 1992 (inclusive) to mothers resident at the time of birth within the geographically defined area of the South East Thames Regional Health Authority (SETRHA) in south east England in order to monitor the children's hip development up to the age of 5 years using serial hip X-rays. It is for this reason that children with hemiplegic cerebral palsy are not included. The South East Thames Health Region at the time had a population of 3.65 million with 205 958 live births during the study period. A comparison of epidemiological data between SETRHA and England and Wales showed similarities between the two. For original methods of recruitment, details of ethical permission and consent, and diagnosis of cerebral palsy the reader is referred to the original paper (Scrutton and Baird 1997).

Present study:

For the purposes of this study, a questionnaire containing details of the child's attainment of bowel and bladder control by day and night, as well as parental concerns or presence of abnormal bladder and bowel symptoms, was used. This questionnaire was administered by physiotherapists to the parents of the children sometime after their third birthdays together with other information required for the original study at that time. The parents/carers were asked to post the questionnaire back to the investigators in a self-addressed envelope. Almost all were returned between the third and fourth birthdays, although one was returned at 5 years. After 5 years of age, a visit was carried out by the original authors, mostly in the child's home together with the parents. A number of parameters were obtained during this visit including confirmation of the diagnosis of cerebral palsy, the nature of the motor disorder including distribution (quadriplegia, diplegia, double hemiplegia and paraplegia) and type (hypertonia, ataxia, involuntary movements, hypotonia and ataxic diplegia after Hagberg 1985), learning level (as ascertained from other medical or educational sources), severity of disability and the age of attainment of bladder and bowel control by day and night. For funding and practical reasons these visits were carried out between 7 to 9 years of age. A closing visit questionnaire, including further continence data was completed some time after the age of 14 years (up to age 19 years) in this cohort, in a similar manner to the above. Whilst the stated aim of this study is to establish the age of attainment of bladder control in subjects with cerebral palsy, data on bowel control have been analysed simultaneously for two reasons: availability and therefore ease of analysis together with bladder data, and the fact that bowel and bladder control are physiologically and developmentally linked, and have been shown by previous authors to follow each other sequentially (Stein and Susser 1967, Largo and Stutzle 1977, Crawford 1989).

Definitions:

Cerebral palsy has been taken to mean all non-progressive disorders of movement and posture caused by a defect or lesion in the brain by 15 months chronological age, and not part of another syndrome which has a motor component. Those with syndromes including a high risk of skeletal or joint anomalies and children whose disorder had no clinical trunk or lower-limb involvement were also excluded. Each child's paediatrician provided written confirmation of the diagnosis at 5 years of age.

Bladder and bowel control was defined as being reliably continent with socially acceptable toileting even if help was required.

Definitions of learning level, severity of disability and type (Hagberg 1989)/distribution of motor disorder are defined and classified according to the Gross Motor Function Classification System (GMFCS).

RESULTS

The results of bladder and bowel continence attainment will be presented in a longitudinal manner together with details of any abnormal patterns which will be discussed. The data collected at three years and eight years of age have already been analysed and analysis of the data available at 16-19 years of age is currently awaited. The only available control comparison group is a series of international studies which are for the large part retrospective, cross-sectional and not population based and neither are they collected from a British population with a similar birth date.

Date proposal received: 
Friday, 11 December, 2009
Date proposal approved: 
Monday, 1 January, 1900
Keywords: 
Neurology
Primary keyword: 

B603 - The effect of common disease associated genetic variants on transcriptomic and early life phenotypes

B number: 
B603
Principal applicant name: 
Dr Dave Evans (University of Bristol, UK)
Co-applicants: 
Title of project: 
The effect of common disease associated genetic variants on transcriptomic and early life phenotypes
Proposal summary: 

ALSPAC has pre-existing data on transcriptomic and phenotype variables related to disease. This is necessary in order to assess the effect of known disease causing variants in early life phenotypes.

Date proposal received: 
Friday, 25 January, 2008
Keywords: 
Primary keyword: 

B2561 - IgG antibody analysis in ALSPAC participants

B number: 
B2561
Principal applicant name: 
Robert Yolken NOTE THIS FORM WAS COMPLETED BY SUE RING |
Co-applicants: 
Title of project: 
IgG antibody analysis in ALSPAC participants
Proposal summary: 
Date proposal received: 
Wednesday, 21 October, 2015
Keywords: 

B3070 - Hypothesis driven analysis of Avon Longitudinal Study early adversity and epigenetic modulation impacting on addiction - 06/03/2018

B number: 
B3070
Principal applicant name: 
Femke Buisman-Pijlman | Adelaide Medical School, University of Adelaide (Australia)
Co-applicants: 
Associate Professor Linda Gowing, Dr Murthy Mittinty, Professor Caroline Relton, Professor George Davey Smith
Title of project: 
Hypothesis driven analysis of Avon Longitudinal Study: early adversity and epigenetic modulation impacting on addiction
Proposal summary: 

Why do people who experience early adversity have a higher chance of developing addiction? Do these experiences leave a biological scar? To answer these questions, we will use information from a group of babies, tracked since birth and who are now in their twenties. We will use new statistical methods and information on their early life, DNA and use of alcohol and tobacco as young adults, to identify which specific experiences change their biology and are linked to development of addiction.

Impact of research: 
We will both advance the statical analysis techniques that can be used to investigate causality and provide information on the relative value of specific early factors on methylation and problematic drug and alcohol use (which will be published in high ranking journals). This will provide good opportunities for assessment and early interventions.
Date proposal received: 
Saturday, 17 February, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Birth outcomes, Epigenetics, Genetic epidemiology, Parenting, Statistical methods

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

B601 - Maternal reproductive history and the outcome of labour

B number: 
B601
Principal applicant name: 
Prof Gordon Smith (University of Cambridge, UK)
Co-applicants: 
Title of project: 
Maternal reproductive history and the outcome of labour
Proposal summary: 
Date proposal received: 
Monday, 14 January, 2008
Keywords: 
Primary keyword: 

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