Proposal summaries
B2357 - How early stress gets under the skin The role of DNA methylation in youth conduct problems and comorbid symptoms - 11/12/2014
Background:
Youth conduct problems (CP; fighting, stealing) are a major public health concern and a key target for prevention and intervention efforts. CP youth often experience high levels of environmental risk (e.g. harsh parenting, family conflict) and psychiatric comorbidity (e.g. depression, ADHD, substance use). Yet, little is known about biological factors that may explain the link between environmental risk, CP and comorbid symptoms.
Aims:
To investigate the role of DNA methylation - an epigenetic mechanism sensitive to environmental influences - in the development of CP and related comorbidities. Specific aims are to: (i) identify methylation markers that are associated with multiple symptoms vs symptom-specific markers; (ii) investigate whether methylation markers cluster to form biologically informative systems; (iii) examine methylation changes in relevant markers over time; (iv) establish whether markers are influenced by pre- and postnatal environmental risk exposure; and (v) test whether methylation mediates environmental effects on CP and comorbidities.
B2356 - 0 New b2356 - 11/12/2014
ALSPAC has the untapped resource of around 10,000 retinal photographs, which are currently being graded. This is an opportunity to analyse and interpret this data to determine what a child's optic disc looks like in the normal UK population. ALSPAC also has the unique benefit of parental data and child data going back to antenatally allowing analysis of factors that influence disk shape and size.
B2355 - Effects of early life residential mobility and key life events on mental health and risky behaviours - 11/12/2014
Project title
Effects of early life residential mobility on mental health and risky behaviours.
Aims
The research project will aim to address the following research questions:
i)Are cumulative residential moves throughout childhood associated with poorer mental health outcomes and increased risky behaviours in adolescence and early adulthood?
ii)Are there critical periods in which the effects of residential mobility on adverse outcomes are disproportionately stronger or weaker?
iii)Do physical characteristics of the move (distance, urban/rural, changing neighbourhood status) mediate effects?
iv)To what extent do background family characteristics and life events exacerbate or attenuate results?
v)Is residential turnover at the neighbourhood level associated with poorer health outcomes?
B2354 - Dietary patterns during pregnancy by cluster analysis and childhood neurodevelopment - 11/12/2014
Dietary patterns during pregnancy and childhood neurodevelopmental. This work is to be the international part of a PhD based in Brazil during this time experience will be gained working in Bristol.
The maternal diet can affect the infant neurodevelopmental (del Rio Garcia et al., 2009; Bernard et al., 2013). The ALSPAC study was explored and there are some studies that assessed the maternal dietary intake of fatty acids (Hibbeln et al., 2007; Hibbeln and Davis, 2009) and 'healthy' and 'unhealthy' food groups (Barker et al., 2013) with childhood neurodevelopmental deficiencies. Dietary patterns have been used in some studies to assess the relationship between diet and health outcomes, because they represent an overview of food and nutrient consumption (Slattery, 2010; Tucker, 2010).
Aim: To obtain clusters of dietary patterns during pregnancy and to examine the association between these dietary patterns and neurodevelopmental outcomes in childhood.
Hypotheses: The adherence to dietary patterns composed by healthy foods can reduce the risk of neurodevelopmental outcomes during the childhood, while the patterns composed by processed food can increase the risk of neurodevelopmental outcomes.
Exposure variable(s): Dietary patterns during pregnancy obtained by cluster analysis.
Outcome variable(s): Neurodevelopmental outcomes in child previously explored in Hibbeln et al. (2007) study. Including clinic measured IQ and parental questionnaire assessed Denver Developmental Screening Test and Strengths & Difficulties.
Confounding variable(s): Maternal education, social class, age at delivery, parity, energy intake, BMI. Child's date of birth, birth weight, sex, gestational age, breastfeeding, child diet at the time of assessment.
We plan to write at least 2 papers as a result of this work. We also have a comparable Brazilian cohort and aim to do some work comparing outcomes in Brazil with ALSPAC outcomes as appropriate.
B2353 - Gender biases in the identification of ADHD - 11/12/2014
Attention deficit hyperactivity disorder (ADHD) is defined by the presence of symptoms of inattention, hyperactivity and impulsivity. To receive a diagnosis of ADHD, six or more symptoms of inattention, hyperactivity and impulsivity must be present for at least 6 months and for children up to the age of 16. Symptoms include difficulties in sustaining attention, difficulties retaining information, difficulties in social etiquette and difficulties with impulse control.
Boys are more likely to present inattentive and hyperactive behaviours compared to girls therefore are more likely to receive a diagnosis of ADHD. Researchers have proposed the ratio of boys to girls with ADHD estimated at between 2:1 and 9:1.
In addition to 'real' differences in underlying symptoms of ADHD, skewed gender ratios could highlight a recognition issue whereby girls are less well-identified and boys are over-identified with ADHD. So the high boys/girl ratios in ADHD diagnosed children are due to a) real differences in symptomology and b) an additional referral or recognition bias. This could be due to girls potentially hiding a childhood history of hyperactivity/disruptive behaviours hence may have not been clinically spotted. Alternatively, it could be because boys typically present more disruptive behaviour therefore more easily spotted than girls, who are more likely to internalize distress.
Other than co-occuring symptoms on which boys and girls with diagnosis differ, differences in cognitive abilities could be potential triggers of referral bias. Higher scores on working memory and processing speed are more pronounced in boys with ADHD compared to girls. If girls with ADHD diagnosis have lower abilities than boys, it may be because they need more severe symptoms before they are referred.
This project highlights a public health concern as gender-sensitive diagnosis could lead to boys being over-diagnosed with ADHD therefore potentially damaging their life opportunities. Also the under-diagnosis of girls may mean they miss out on treatments that would benefit them. This project aims to investigate this gender bias in the identification of diagnosing ADHD.
B2352 - ICMR-MRC joint initiative aetiology and life-course of substance misuse and relationship with mental illness - 11/12/2014
The proposal is being developed. The main purpose is to develop cohorts in India and compare risks and exposures for developing substance use and mental health problems between India and UK - using ALSPAC and IMAGEN.
Background:-
In both, developed and emerging nations externalising behaviours are known to be risk factors for substance abuse and substance abuse is highly correlated with externalising disorders. Environmental risk factors for substance abuse, its relation to externalizing behaviour and its moderation by genetic and epigenetic factors have not been extensively investigated in emerging societies. Given that emerging societies show the biggest increase in alcohol and tobacco use, there is an urgent need to validate and adapt our understanding of etiology and determinants of substance abuse in these countries. Here we compare insights into etiology and trajectories into substance abuse gained from two major European and UK studies, IMAGEN and ALSPAC with Indian cohorts of different social and environmental backgrounds. We will also control for socio-cultural and environmental influences by investigating determinants of substance abuse in SCAMP, a UK cohort containing adolescents of both, European and South Asian descent.
Our project capitalizes on existing cohorts in India with over 18.000 participants, which it aims to enrich using the expertise and infrastructure created by the individual teams. The cohorts have been selected to allow an accelerated longitudinal design covering an age range of 0 to 25 years. These assets will be complemented by European and UK cohorts of approximately 20.000 participants, including IMAGEN (www.imagen-europe.com), ALSPAC and SCAMP, which have established the relevant neuroimaging, neuropsychological, behavioural and clinical assessments which will be applied in our project. As the ongoing SCAMP projects will recruit greater than 1000 13 year old adolescents of South Asian origin we will harmonize the assessment of our study and SCAMP. Together with data available in IMAGEN and ALSPAC this will allow the most comprehensive comparative analysis of brain development and behaviour in different social and cultural environments. In addition, we will use candidate gene sets identified in large GWAS meta-analysis consortia of over 300.000 participants, including ENIGMA, Alcogen and the Psychiatric Genetics Consortium, which are relevant for addictive behaviour and externalising symptoms. Using these assets we will test the following hypotheses:
a.)Exposure to environmental risk or resilience factors, which are pertinent to emerging societies both ante-natal as well as throughout childhood and adolescence are correlated with structural and functional impairments of reinforcement-related brain function, and externalizing behaviour including addictions. These risk factors include (but are not limited to) socio-cultural environment, psychosocial stress, malnutrition and exposure to neurotoxins,
b.)Environmental risk factors influence epigenetic methylation profiles and interact with candidate genotypes across the developmental span, altering development trajectories of growth and brain development, which give rise to variations in temperament and addictive behaviours. Relevant measures include birth weight, anthropometric -somatic and endocrinological measures, brain endophenotypes, cognitive abilities, temperament.
c.)Susceptibility to substance abuse and externalising disorders is dependent on ethnicity and/or socio-cultural influences in comparisons between UK and Indian cohorts
B2351 - Studies of telomere length and mitochondrial DNA copy number in association with age-related phenotypes within ALSPAC - 11/12/2014
Telomeres, the protective caps at the end of chromosomes, shorten with every cell division. Dysfunction of the maternally inherited mitochondrial genome leads to oxidative stress, and the genome is copy-number variable, with more copies in tissues with higher energy requirements. Damage to both telomeric and mitochondrial DNA contributes to cell signalling via p53-mediated pathways, leading to cellular senescence and apoptosis (programmed cell death). Telomere shortening, and mitochondrial dysfunction are therefore known mechanisms of cellular ageing, and recent studies have suggested that mtDNA copy number and leucocyte telomere length (LTL) may be related (Passos et al., Sahin et al.). Telomere length is related to diseases involving accelerated ageing, including those in which inflammation, oxidative stress and disordered cell turnover have been proposed as important: such diseases are cardiovascular disease (Haycock et al.), respiratory disease (Albrecht et al.), and putatively, psychosis (Nieratschker et al). Whilst classical risk factors related to these diseases may also associate with LTL/mtDNA copy number, inflammation may act as a global risk factor for them all, and LTL/mtDNA copy number may mediate these associations (Masi et al.).
We propose to measure average LTL in ALSPAC mothers and children using qPCR, and to perform downstream analyses on the dataset generated. By studying young people, we may analyse telomere length and mtDNA copy number as mediators of associations between early risk factors of chronic disease (e.g. growth trajectories (Barker, 2003), and inflammation) and outcomes, before a large burden of classical risk factors are accrued. Genomic control of these traits, including imprinting effects, will be assessed using mother-child pairs. As well as assessing prior hypotheses, we propose to perform phenome scans of LTL and mtDNA copy number. Ultimately, this proposal aims to understand the relationships between LTL and mtDNA copy number, and their contribution, individual or combined, to senescence.
Hypotheses:
1.Average telomere length will be shorter in ALSPAC mothers compared to offspring, and children's average telomere length will decrease with age.
2.SNPs that may be associated with telomere length may have small effect sizes. Controlling for parent-of-origin effects may unmask these effects.
3.LTL will correlate with phenotypes of accelerated ageing, inflammation or oxidative stress.
4.Telomere length will be related to foetal and childhood growth, biomarkers of growth (GHBP/IGF1) and pubertal stage (as measured by Tanner stage/testosterone).
5.Telomere length will correlate positively with mtDNA copy number.
6.Given the fundamental role of telomeric and mitochondrial dysfunction in senescence, as-of-yet unidentified phenotypes will be associated with these 'genetic phenotypes'.
Aims:
1.To assess average LTL in the Avon Longitudinal Study of Parents and Children.
2.To perform a genome-wide association study of LTL/mtDNA copy number in children, and to assess mother-offspring pairs for parent-of-origin effects.
3.To study telomere length and mtDNA copy number in relation to diseases involving accelerated ageing processes (cardiovascular disease, COPD/asthma, and putatively, psychosis/depression), risk factors for these diseases (e.g. classical CVD risk factors, smoking, inflammation), and intermediate disease phenotypes (e.g. spirometry, psychosis-like symptoms).
a.To refine these associations in individuals with extreme phenotypes.
4.To investigate LTL changes in relation to foetal and childhood growth and puberty.
5.To study the association between telomere length and mtDNA copy number.
6.To undertake phenome scans of LTL/mtDNA copy number (and genetic variants determining them) to determine novel associations.
B2349 - Identifying Parent -of -origin effects POE on birth weight - 04/12/2014
Aim: to replicate genetic associations showing parent-of-origin effects (POE) on birth weight, following initial analysis of UK Biobank data.
Proposal: Monogenic disorders of imprinted genes (e.g. IGF2/H19 disruption in Beckwith-Wiedemann syndrome or Silver-Russell syndrome) often show marked effects on birth weight. However, the role of imprinting (i.e. where the influence of an allele depends on whether it is maternally- or paternally- inherited) in common variation in birth weight is unknown. We hypothesise that there will be common variants at genetic loci which show POE on birth weight, and that known imprinted regions of the genome are enriched for these variants. Recently a method was published to investigate parent of origin effects (POE) in large genome-wide association study (GWAS) datasets of unrelated individuals (Hoggart et al 2014 PLoS Genetics).
We will be applying this method to the forthcoming GWAS data on birth weight in UK Biobank to identify POE across the genome, and to test whether POE on birth weight are more likely to occur in known imprinted regions.
Any loci showing evidence of association will require replication in independent studies. Ideally these studies would have mother, father and child genotype available, but there are few studies with these data. It is possible to gain a large amount of information, however, from the analysis of mother-child pairs. ALSPAC represents the best study in which to do this. We propose to replicate the identified loci from UK Biobank in ALSPAC and potentially other available studies including EFSOCH and HAPO. The replication sets will not have the statistical power comparable to Biobank but will have better quality phenotype data, the presence of maternal genotypes and will enable comparison of effect sizes of the associations observed in Biobank.
B2348 - Are Children with Impaired Vision or Hearing at Greater or Differential Risk of Unintentional Injury - 04/12/2014
The aim of my research is to investigate the extent to which visual impairment (VI) or hearing impairment (HI) affects a child's risk of unintentional injury (UI), and the association of that UI with a range of child, family and environmental factors. A systematic review I carried out demonstrated a paucity of studies, with the highest level of evidence found being case control studies. UI is a leading cause of morbidity and mortality for children, with the major global childhood UI killers being road traffic injury, drowning, fire related burns, falls and poisoning. Some of these areas of key interest to my research were not looked at by any studies, including drownings and fire-related injuries. Only one paper dealt with road traffic injuries, and only two case reports looked at poisonings. The severity of impairment, dental injuries, activity levels and effect of co-morbidity were described as needing higher level research.
No epidemiologically robust population-based cohort studies were found. The ALSPAC study has already collected detailed longitudinal data on sensory impairments and all the major childhood unintentional injuries, as well as a wide range of other relevant factors such as socioeconomic circumstances. The data is highly relevant to my area of research interest with detailed vision variables at age 7 and 11, detailed hearing variables at age 7, 9 and 11 and detailed unintentional injury variables at 5, 7, 11 and more specialised data at 13 and 16.
B2347 - Matching in the marriage market evidence from ALSPAC - 04/12/2014
Background:
In this study we will investigate how mothers' choose their partners. We will investigate this matching process using the exemplar of the relationship between parents' heights. Parents' heights are more associated than would be expected if individuals mated randomly within the population (Silventoinen et al. 2003). Height is a highly heritable phenotype. We do not know how much of the association of partners' heights is due to a genetic correlation, and how much is due to individuals from similar environmental backgrounds matching. For example, the associations of partners' heights could be because they chose to mate with individuals with similar backgrounds. We will extend the Mendelian randomisation framework to address these questions.
ALSPAC is an ideal dataset to investigate this hypothesis because it has detailed longitudinal data on both mother and fathers of the cohort children and genome-wide data on a large sample of the mothers.
Aims:
We will estimate the associations between mothers' height and height allele scores and their partners' height and observable characteristics using ALSPAC data.
Hypothesis: What are the associations between mothers' height and genotypic scores for scores for height and their partners' observed height and characteristics?
Exposure: The mothers' height at birth of their child and a weighted allele score of 697 recently reported height variants will be used as the exposure.
Outcomes: The outcomes will be the fathers' height, education, family income, paternal grand-parents education.
Confounding variables: first eight principal components of population stratification.
Outline:
People do not choose their partners at random: partners tend to be more similar than would be expected if partners were randomly chosen. We do not know if these associations are because people directly match on particular characteristics, height for example, or because partners match on a third confounding factor, such as their socio-economic background. We will investigate these associations in ALSPAC. There are now 697 genetic variants which are known to affect height (Wood et al. 2014). We will use these variants as instrumental variables for mothers' height in a Mendelian randomisation analysis.
In this study we will investigate the observed association between the mothers' height and their partners' phenotypes and compare the size of this association to the association implied by the genetic variants for height. If individuals actively match on height then we would expect similar associations between the observed height and the genetic variants for height. However, if the observed associations between mothers' height and their partners' phenotypes are the result of a third, confounding factor, then we would expect to find weaker evidence of associations between the genetic variants and the partners' characteristics. To maximise power we will construct weighted allele scores of the height genetic variants.
B2346 - Understanding variability in cardio-metabolic risk in the ALSPAC cohort - 27/11/2014
Objectives
Primary: 1) To investigate the association between birth order and measures of adiposity (BMI; waist circumference and fat mass, change in fat mass from 9 to 15 years), metabolic (fasting glucose, fasting insulin and lipid profile) and vascular (blood pressure) functions at 15 years old male and female adolescents enrolled in the ALSPAC cohort. 2) A diagnosis of metabolic syndrome will be performed based on measurement of waist circumference, fasting glucose, triglycerides, HDL, blood pressure and the relative risk for metabolic syndrome at age 15 associated with being first-born compared to later-born children will be assessed.
Secondary: We shall test for sex-differences in these associations.
B2345 - Association of atopic illness and raised inflammatory markers in childhood with manic symptoms in young adult life - 27/11/2014
Background:
Previous research using the ALSPAC cohort has found an association between childhood serum levels of interlukin 6 (Il-6) and C-Reactive Protein (CRP), and both depression and psychosis symptoms in young adult life (1). The association between childhood inflammatory markers and bipolar disorder has not been examined. There is some evidence that Il-6 is acutely raised during mood episodes in bipolar disorder but appears to return to control levels during euthymia (2). Also there are reports that inflammatory illnesses in childhood, such as asthma, are associated with both elevated Il-6 prior to the diagnosis (3) and with adult diagnoses of bipolar disorder (4).
Aim:
To examine the association between atopic illness (asthma and eczema) and inflammatory markers in childhood, and manic symptoms in young adult life.
Hypotheses:
1) That atopic illness in childhood is associated with increased risk of future manic symptoms
2) That higher serum levels of Il-6 and CRP in childhood increase the risk of future manic symptoms.
B2344 - Investigating the possible bidirectional association between smoking and caffeine using Mendelian randomization - 27/11/2014
Aims
To investigate the possible bidirectional association between smoking and caffeine consumption using Mendelian randomization.
Hypotheses
Coffee consumption and cigarette smoking are highly comorbid [1]. Observational studies suggest that coffee drinkers are more likely to be smokers than non-drinkers [1, 2], and also suggest a positive association between coffee consumption and cigarette consumption [3], and an inverse relationship between coffee consumption and smoking cessation [4].
However, the causal nature and direction of these effects are unknown and are difficult to infer from observational studies. Mendelian randomization methods minimise bias from confounding and remove the possibility of reverse causality [5].
Genetic variants for both smoking behaviour phenotypes and coffee consumption have been identified in genome-wide association studies [6, 7]. These can be used as instruments for measured coffee consumption and smoking behaviour in Mendelian randomization studies. Polygenic risk scores for these exposures can be generated from GWAS data to increase the power of Mendelian randomization analysis [8].
Polygenic risk scores for smoking behaviours and caffeine consumption will be generated from GWAS data for both the ALSPAC mothers and ALSPAC children. We will investigate the associations of genetic risk scores for smoking with caffeine consumption and the association of genetic risk scores for caffeine consumption with smoking. These analyses will be run in parallel with data from the Netherlands Twin Registry.
B2343 - The exploration of an association between previously reported orofacial cleft genes and lip trait phenotypes - 27/11/2014
The aim of this study it to explore a link between specific genes that have been reported to be associated with orofacial clefting and identified lip traits from 3D facial scans.
We hypothesise that SNP's associated with clefting, should have an effect on lip morphology. The exposure variable is the orofacial cleft gene carrier (see appendix for list of candidate genes) and the outcome variable is the characteristic lip trait (see categorisation table) - that may have increased/decreased occurrence of certain features. These features may in turn be considered risk factors in determining risk of orofacial clefting.
The GWAS for these lip traits has already been conducted (under B568) and so this proposal should just involve the look-up of the relevant variants in those results. Lavinia Paternoster (IEU) has access to these results. These look-ups and any subsequent analysis required will be carried out by Caryl Wilson-Nagrani as an IEU temporary visitor under the supervision of Lavinia Paternoster.
B2342 - Associations of Behaviour Disorders in Childhood and Psychotic-Like Symptoms in Adolescence - 27/11/2014
Associations of Behaviour Disorders in Childhood and Psychotic-Like Symptoms in Adolescence
The general aim of the project is to analyze the associations between childhood behaviour disorders and psychotic symptoms in adolescence. Many adults with psychotic symptoms and/or schizophreniform disorders received a psychiatric diagnosis in childhood. These diagnoses cover the full range of developmental, internalizing, externalizing, and behavioural disorders (Rubino et al., 2008). To date, it is not clear whether the presence of childhood mental symptoms and disorders as such represents a general risk factor for later psychopathology or whether there are specific associations indicated by stronger correlations for some disorders (research question 1) and how these associations are characterized (research question 2).
B2341 - Role of rare coding variants in speech and language disorder - 20/11/2014
AIM - to investigate the contribution of rare coding variants in selected candidate genes to speech and language disorders
BACKGROUND
Our lab investigates genetic contributions to speech and language disorders, primarily within a cohort of families in which at least one child is diagnosed with specific language impairment (The SLI Consortium (SLIC) cohort). Investigations in this cohort have highlighted specific genetic pathways and candidate genes that we believe might be linked to speech and language development. We would like to follow these genes up in more detail in a larger cohort. The effects we have identified are rare coding mutations. In order to follow these up, we therefore need access to a large cohort in which speech and language data and genetic sequencing are readily available.
B2339 - Investigation of the association between birth weight reproductive abnormalities and placental function - 20/11/2014
Background
Amongst disorders of sex development (DSD) cases, conditions associated with under virilisation of the presumed XY boys are the largest group of children. Our international group (I-DSD.org) recently reported in Pediatrics that this group of people will increase as more affected infants are raised as boys. XY DSD boys often have low birth wt and are also often small for gestational age (SGA), as confirmed by Hughes et al, Cambridge using the ALSPAC cohort. Altered exposure to androgens has been linked with DSDs, intra-uterine growth restriction (IUGR) and placental problems, possibly all involving the IGF signalling pathway. For example, exposure to exognous androgens in sheep advances placental differentiation and increases placental differentiation but this early compensation to maintain placental efficienc cannot be mainted long term leading to placental inefficiency and IUGR. Furthermore, altered steroid exposure in fetal rats through exposure to MPA, a synthetic progestogen, reduced external genitalia masculinisation in males and increased it in females, and reduced bodyweight and placental weight in both males and females.
Aims
We hypothesise that:
(1) Boys with DSDs (namely hypospadias and/or cryptorchidism) are more at risk of being SGA, possibly due to altered placental development and/or funtion.
(2) The SGA phenotype associated with DSDs, such as hypospadias, is different to the SGA phenotype without hypospadias.
(3) Boys with hypospadias may have been denied sufficient androgen exposure prenatally and/or experience an ongoing lack of androgens, which may have a negative impact on their future health and well being.
We therefore propose to analyse the ALSPAC data for variables such as birth weight, gestational age at birth, placenta weight, congenital abnormalities at birth such as hypospadias, anogenital distance in the child, any fertility treatment prior to pregnancy, as well as moderately long-term outcome that relates to height, cardiometabolic and body composition including skeletal health.
We wish to compare the following groups - hypospadias and SGA, SGA and no hypospadias, average GA and hypospadias and AGA and no hypospadias. We may also be interested in the same analysis for individuals with cryptorchidism
B2338 - Ascertaining direction of causality in associations between smoking cognition and schizophrenia - 20/11/2014
Aims:
Associations are consistently seen between cigarette use and psychosis, although direction of causation is not known. There is also a large body of literature showing cognitive impairment in patients with schizophrenia. There has been some suggestion that high rates of smoking in schizophrenia could be to alleviate cognitive impairment from both the disorder and anti-psychotic medication side-effects, as nicotine has been posited as a cognitive enhancer. We aim to investigate whether associations between cigarette use, cognition and psychotic experiences are causal, using Mendelian Randomisation.
Hypotheses:
As these are exploratory analyses, we do not have hypotheses as to what we will find in terms of causality.
Exposure variables:
Genetic instruments as proxy variables for cigarette use and for risk of schizophrenia.
Outcome variables:
Cognitive tasks at age 18, smoking at age 18, psychotic experiences at age 18 (all measured at clinic).
Confounding variables:
As this is a Mendelian randomisation design, the analyses should not be subject to the usual confounders that impact upon observational studies. However, gender and ethnicity will be accounted for in our analyses. Data on confounders has been requested to check for pleiotropy.
B2337 - The association between caffeine consumption during pregnancy and birth weight a Mendelian randomization study - 20/11/2014
Aim
To investigate if maternal caffeine intake during pregnancy causally influences offspring birth weight using a Mendelian randomization approach.
Hypotheses
A recent meta-analysis of observational studies found evidence that caffeine consumption during pregnancy is associated with increased risk of having a low birth weight baby [1]. However, it is not clear whether this association is causal or whether this may be due to confounding by other lifestyle factors. For example, coffee consumption is positively correlated with cigarette consumption, a known risk factor for low birth weight [2].
This problem of confounding can be minimised using Mendelian randomisation analyses, whereby genetic variants associated with caffeine are used as proxies for measured caffeine consumption. Genome-wide association studies have identified 8 independent genetic loci associated with coffee consumption [3, 4]. Some of these variants have been shown to associate specifically with caffeinated beverage intake in ALSPAC [5].
This project will investigate associations between maternal caffeine-related genetic variants and offspring birth weight using a Mendelian randomisation approach.
B2336 - Enhancing data collection in ALSPAC-G2 using novel methods A feasibility study - 20/11/2014
Background:
A high proportion of women start pregnancy overweight/obese. According to the developmental overnutrition hypothesis, this could cause offspring to be fatter throughout their lives, and therefore, this may perpetuate the obesity epidemic across generations.1, 2 Concerns about this hypothesis are influencing antenatal care. Two key changes to antentatal care which have occurred in relation to concerns about developmental overnutrition are:
1.Monitoring weight throughout pregnancy. This was previously done with the aim of identifying those at risk of SGA, but was stopped in the mid-1990s because of evidence of its poor predictive value.3 It is now being done with the intent of limiting gestational weight gain (GWG) in order to prevent women having infants who are LGA, since they may go on to be more adipose throughout their lives.4
2.The new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for defining gestational diabetes (GDM), which have been adopted by the WHO, aim to identify those at risk of LGA and greater offspring adiposity.5
However, whether the associations of maternal adiposity with offspring outcomes are causal is unknown, and if they are indeed causal, then the mechanisms are unclear.1, 2 Being able to accurately quantify maternal and fetal fat mass, glucose variability, diet, physical activity and a wide range of potential circulating nutrients in women during pregnancy could clarify the effects of maternal overweight/adiposity on her future health and that of her offspring. Having tools for obtaining these data that are acceptable, feasible, cost-effective and safe in pregnancy would support translation of research findings into clinical practice as appropriate.