Proposal summaries
B2221 - Maternal function folate status and risk of ASDs in the ALSPAC birth cohort - 10/04/2014
Aims
In our proposed work, we aim to investigate relationships between ASD and related traits, and key determinants of functional folate-status in a large, well-characterized birth cohort with prospectively collected data. Determinants of folate-status to be investigated include self-report of maternal folate supplementation at 16 and 32 weeks gestation, dietary folate intake at 32 weeks gestation, child folate intake reported at 1 year of age, as well as maternal and child genetic variants involved in one-carbon metabolism and epigenetic regulation. These determinants are to be investigated both individually, and jointly to assess potential interactions.
B2220 - Does early frequency and form of stools predict later bowel and bladder dysfunction and their consequences - 10/04/2014
To establish if early questionnaire data on frequency and form of stooling predicts future bowel and bladder dysfunction in children. This data will be ised to model the costs and benefits of treating infants and children for long periods with stool softeners to reduce the incidence of constipation, soiling and daytime wetting.
B2219 - The role of DNA methylation in the aetiology of type 2 diabetes - 10/04/2014
AIMS
The proposed project aims to investigate the relationship between increased risk of type 2 diabetes and methylation profile. Specifically:
1. Is variation in DNA methylation associated with risk of type 2 diabetes?
In ALSPAC mothers, individuals will be selected based on high and low risk of developing type 2 diabetes (using measures of glucose and insulin, metabolomics data, diagnoses of gestational diabetes or repeated measures of glycosuria during pregnancy). We will then look for associated patterns of DNA methylation.
2. Can DNA methylation signatures predict who progresses to type 2 diabetes and/or other co-morbidities (cardiovascular disease) from those who will not?
Using follow-up data from ALSPAC mothers (FOM) we will investigate if methylation status at baseline has any predictive influence on which individuals developed adverse health outcomes (type 2 diabetes or worsened metabolic profile). DNA methylation measures at follow-up will identify methylation differences over time and may also identify loci associated with later health adversity.
3. How do genetic variation influence methylation patterns?
At methylation loci of interest (following discovery in aims 1&2) we will identify any relationship between methylation and measured genetic variants. This will help us to understand by how much methylation patterns are determined by the underlying genetic sequence.
4. To utilise genetic sequence-methylation associations in order to distinguish between non-causal biomarkers and causal pathways
The causal/non-causal relationships between genotype, DNA methylation and metabolic measures will be investigated using Mendelian randomisation. Using genotype information from objective 3, SNPs that correlate highly with methylation at CpG sites of interest will be utilised as 'proxy' measures of DNA methylation. This permits the use of genotype data and therefore the relationship between (proxy) methylation and outcome of interest can be evaluated.
B2226 - Birth weight and metabolomics profiles through the lift-course Meta-analysis of 20000 people - 10/04/2014
Aims:
Low birth weight is linked with an adverse metabolic profile in adulthood and increased risk for cardiometabolic diseases. We aim to elucidate this relationship by examining associations of birthweight with a comprehensive metabolite profiled quantified by high-throughput serum NMR spectroscopy. We will assess associations of birthweight (as continuous measure) with uniform data on serum metabolites in greater than 20,000 individuals from several population-based cohorts from Finland, and would like to include ALSPAC in the analyses. ALSPAC has recently completed high-throughput metabolite profiling by NMR for multiple time-points in both the children and the mothers. The multiple time-points metabolite data in ALSPAC will be examined for effect modulation by age, ie. if effects of birthweight are fixed during adolescence and early adulthood. Similar multiple time-points is available for 2 Finnish cohorts.
B2225 - Patterns in the size timing and frequency of food and drink consumption and diabetes risk in young adults - 10/04/2014
Aim:
To systematically assess variation in the size, timing and frequency of consumption within a day, from day-to-day and across the lifecourse and how it relates to diabetes risk at 25 years of age and change in diabetes risk from 15 to 25 years of age.
B2223 - Chronic irritability in ADHD Examining clinical and genetic links with depression - 10/04/2014
Aims:
The proposed project aims to use data from the ASLPAC study to test whether:
1. In children with ADHD, symptoms of irritability are associated with an increased risk of depressive symptoms in adolescence.
2. In children with neurodevelopmental disorders (including ADHD, Intellectual Disability (ID), Autistic Spectrum Disorder (ASD), Communication Disorders, Motor Disorders), symptoms of irritability are associated with an increased risk of depressive symptoms in adolescence.
3. In children with ADHD and other neurodevelopmental disorders, symptoms of irritability index higher rates of family history of depression and increased genetic risk for depression.
B2222 - Does body dissatisfaction cluster in schools - 10/04/2014
Aims and Objectives
The aim of my project is to increase understanding of eating disorders (ED) and body dissatisfaction (BD) in adolescent girls from the perspective of population-level pathways.
Understanding whether ED and BD cluster in schools would inform the development of school-level interventions to reduce incidence of ED. No studies have investigated whether ED and BD cluster, despite the clinical observation that it appears to be the case, although disordered weight control behaviours do vary between schools. Preliminary results from the Swedish cohort described below suggest around 9% of variance in rates of ED is at school level.
B2218 - Pathways to positive and negative sexual health outcomes in young adulthood ALSPAC at 24 - 03/04/2014
Sexual behaviour is a normal part of human development, and sexual health is a central component of physical and mental health. However, sexual activity can also lead to adverse health consequences including sexually transmitted infections (STI) and unintended pregnancies, whose impact may be profound and long lasting. Intimate relations may also be the setting for violence between partners with wider health consequences for families. In the UK and elsewhere the above adverse outcomes are common and may be increasing, in part reflecting deficiencies in intervention policies. The UK Government has specified improving sexual health as an overarching priority. Sexual behaviour associated with increased risk of adverse sexual health outcomes may be influenced by the dynamic interplay of biological, individual, social, cultural, environmental and political processes across the life course. In particular, sexual development takes place in the context of developing social, peer and romantic relationships. It follows that an understanding of the development of young adult sexuality and other risk-taking behaviours and the association between these behaviours and outcomes such as STI requires longitudinal data about early and middle childhood experiences, as well as accurate data about the onset of romantic, sexual, and risk-taking behaviour from late childhood onwards. Such understanding is key to the design of appropriate public health interventions to improve sexual health. If the causal roots of risky sexual behaviour and its adverse sexual health consequences lie early in the life course then this is where effective intervention should be targeted. However, it may be that risk of adverse sexual health outcomes is substantially determined by proximal factors essentially independent of the pathways that precede them. This possibility has different implications for prevention. It may also be the case that most risk of adverse sexual health outcomes is not primarily attributable to a definable syndrome of risky sexual behaviour. Finally it is important to investigate the predictors of positive sexual health outcomes as these may also have implications for effective health promotion.
Investigation of these hypotheses, and their different implications for prevention, calls for general population based studies of adolescents at an age where a sufficient proportion is sexually active with prospective data both on sexual behaviour, its correlates and antecedents and on sexual health outcomes. ALSPAC is one of the few studies internationally, and the only study in the UK, currently able to support such investigation
Objective 1: To measure patterns and prevalence of sexual behaviour and related risk behaviours at age 24
Participants attending the clinic will be invited to complete a validated computer assisted self-interview (CASI), covering sexual behaviour, attitudes and lifestyle (including age at coitarche in non-virgins, circumstances of first intercourse, whether activity was regretted, condom and other contraceptive use, pregnancy and parenthood, use of pornography, other 'romantic relations', intimate partner violence, and positive sexual experiences. Questions used will be the same as in previous assessments to maintain consistency and allow estimation of incidence with more detailed questions on current sexual lifestyle appropriate for young adults also included.
Objective 2:To estimate the age-specific prevalence and incidence of genital Chlamydia, Mycoplasma, and Gonorrhoea in a birth cohort of UK adolescents.
ALSPAC participants attending the age 24 clinic assessments will be invited to submit a first catch urine specimen, which will be tested for the presence of the above infections, and a blood sample, which will be tested for the presence of chlamydia antibodies. Permission will also be sought to test stored blood and urine samples collected at previous clinic assessments between the ages of 11 and 15.
Objective 3: To investigate pathways to both positive sexual health outcomes and risky sexual behaviour and adverse sexual health outcomes from early life to adolescence in a birth cohort of UK adolescents
Objective 4: To investigate life course influences on use of sexual health services and participation in Chlamydia screening
Objective 5: To investigate the validity of serological testing as a measure of lifecourse exposure to genital Chlamydia trachomatis
Objectives 4 & 5 will use data obtained from linkage between ALSPAC and the PHE CTAD database.
Objective 6: to collect information on sexual networks to inform modelling of the transmission dynamics of common STI.
We will examine four broad hypotheses
a.) Risky sexual behaviour is an important independent risk factor for adverse sexual health outcomes.
b.) Other problem behaviours and outcomes (substance use, antisocial behaviour, low educational attainment) are important independent risk factors for risky sexual behaviour.
c.) There is a causal pathway from early life adversity and childhood problems to risky sexual behaviours, mediated through other problem behaviours in adolescence (substance use and/or antisocial behaviour and/or low educational attainment).
d.) Early life adversity, childhood problems, and other problem behaviours in adolescence are associated with STI infection.
A key issue in making inference about causal relations between variables such as those in the above diagram is clarification of the extent of socio-economic confounding. Many associations between different adverse health and social outcomes are likely to reflect their covariance with social disadvantage, rather than a distinct causal pathway. Some of these relations, however, may mediate the association between social disadvantage and poorer health. We will add, in turn, potential confounding variables related to (1) early life adversity and childhood socioeconomic circumstances; (2) childhood psychosocial problems; (3) other variables relating to problem behaviours in early adolescence; and finally (4) behavioural variables measured concurrently with sexual behaviour and sexual health outcomes. In considering the choice of possible confounding variables we will follow the approach of Hernan and colleagues who point out that strategies based on knowledge of the causal structure are more appropriate than those based on statistical strength in choice of confounding variables. We will use multilevel models as appropriate, to include repeated measures on each individual (for example to reflect changing socio-economic circumstances).
B2217 - Do parental child and home environment factors mediate the association between socioeconomic status and injury - 03/04/2014
AIMS:
Research has consistently shown that children of low socioeconomic status (SES) are at an increased risk for injury. However, the mechanisms of this association are not fully understood.
Factors such as poor parental supervision, behavioral problems in children, and unsafe housing have been associated with increased risk of injury. Prior studies using the ALSPAC data have found that various social and environmental characteristics such as living in a single parent home, parental depression, living in an unsafe neighborhood, and presence of safety hazards in home can contribute to injury in children four years of age and younger (1-3). Findings from Reading et al. indicate that individual characteristics of children and parents explain neighborhood clustering of injury rates (2), however, the degree to which these factors explain socioeconomic variation in injury is not fully understood.
The aim of the current study is to examine whether parental, child, and home environmental factors mediate the association between family socioeconomic status and injury in young and school aged children.
HYPOTHESIS:
It is hypothesized that child characteristics, parental characteristics, and quality of the home environment will mediate the association between socioeconomic status and injury.
EXPOSURE/MEDIATING VARIABLES:
Family income, housing characteristics (e.g., type of home, age of housing, home hazards, number of times the family has moved, neighborhood safety), parental/supervision factors (parental education level, general physical health, depression, alcohol use, exposure to traumatic events, size of family, marital status of parents), and child characteristics (age, gender, race/ethnicity, behavior/temperament).
OUTCOME VARIABLES:
Child accidents and injuries (types of injury, how/where occurred, severity of injury)
B2216 - Pregnancy complications menopausal transition and metabolomics - 03/04/2014
BACKGROUND
1. Pregnancy complications and subsequent metabolic profiles in mid-life.
Pregnancy complications, including hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), preterm birth, small for gestational age (SGA) and large for gestational age (LGA) are associated with subsequent increased cardiovascular and diabetes risk in the mother, though the precise mechanims underlying these associations are unclear.[1] In ALSPAC we have previously shown that HDP is associated with a wide range of cardiometabolic risk factors (greater body mass index, fat mass, waist circumference, blood pressure and fasting lipid levels and adverse fasting lipids) approximately 18 years postnatal, whereas GDM was associated only with greater fasting glucose and insulin. However, both were associated with the same increased risk (~30%) of predicted CVD based on the Frammingham equation.[2] Preterm birth and SGA were associated with higher blood pressure 18 years later and LGA with higher waist circumference and fasting glucose.[2]
A number of small studies (commongly fewer than 100 participants) have shown that blood based metabolites (either maternal gestational or fetal assessed in cord blood), including amino acids, fatty acids, lipids and phospholipids, are associated with pre-eclampsia.[3-8] One study found differences in sphingolipids, phospholipids, carnitines and fatty acids in early pregnancy maternal serum comparing those who had a SGA infant to those with a normal for gestational infant,[9] and one differences in cord-blood glucose, several amino acids, lipids and lipoproteins between infants of mothers who did, and those who did not, have GDM.[10] To our knowledge no study to date has examined the relationship of pregnancy complications with future metabolic profiles in the mother some years after delivery and the extent to which these might explain any association of these complications with atherosclerosis.
2. Menopausal transition and metabolic profiles
There is increasing interest in the role of the menopausal transition and health ageing in women.[11,12] Endogenous oestrogen levels are cardioprotective and a large number of cross sectional studies have shown that cardiovascular events and risk factors are higher in women who are post- compared to pre-menopausal.[13] From the small number of relatively small (N ~ 50 to 1000) studies with repeat measurements of cardiovascular risk factors there is evidence that as women go through the perimenopausal transition adiposity, fasting glucose, insulin, LDLc and triglycerides increase and HDLc decreases independently of age-related changes, whereas blood pressure changes at this time appear to reflect age effects.[13] Recently a meta-analysis of cross sectional associations in greater than 10,000 participants
found metabolic profile differences between women and men, with a sex*age interaction that supported adverse (in relation to atherosclerosis) changes in women around the time of the menopausal transition. In cross-sectional analyses in a subgroup of the women they showed adverse levels of lipids, lipoproteins, fatty acids and amino acids in between age matched women who were pre-, peri- and postmenopausal.[14] To our knowledge no one to date has examined prospective associations of menopausal status and change in this with change in metabolic profiles.
OBJECTIVES
1. Pregnancy complications and subsequent metabolic profiles
1. To determine the associations of HDP, GDM, preterm birth, SGA and LGA with subsequent (~18 years later) metabolomic profiles, including identifying the extent to which the different pregnancy complications overlap with each other in terms of relating to similar future metabolic disruptions.
2. To determine the cross-sectional association of metabolic profiles with atherosclerosis, as measured by cIMT, in middle-aged women.
3. To determine the extent to which metabolic profiles mediate any associations of complications of pregnancy with future cIMT
2. Menopausal transition and metabolomic profiles
1. To determine the cross-sectional associations of menopausal status and hormone use (women will be categorised into mutually exclusive categories of: hysterectomy/oophorectomy; using HRT; using hormonal contraception; pre-menopausal; in menopausal transition; early post-menopause; late post-menopause, according to STRAW criteria for menopausal/reproductive status) with metabolic profiles.
2. To determine the prospective change in menopausal status with change in metabolomic profiles.
METHODS
1. Pregnancy complications and metabolomic profiles
For this paper obstetric and early pregnancy questionnaire data will be combined with data from FoM1
Analyses will be done by Qin Wang with supervision from Mika Ala-Korpella and Debbie Lawlor
2. Menopausal status and metabolomic profiles
For this paper data from FoM1 and FoM2 will be primarily used
Analyses will be done by Qin Wang (as above)
Data preparation
Debbie Lawlor will work with Kate Northstone to put some of the non-metabolomic data together, Kate / someone from her team will link these data to the metabolomic data and add a research collaborator number before they are transferred to Mika Ala-Korpella at the University of Oulu.
REFERENCES
1. Rich-Edwards JW, Fraser A, Lawlor DA, Catov JM. Pregnancy Characteristics and Women's Future Cardiovascular Health: An Underused Opportunity to Improve Women's Health? Epidemiol Rev 2014; 36: 57-70
2. Fraser A,
3. Kenny LC, et al. Novel biomarkers for pre-eclampsia detected using metabolomics and machine learning. Metabolomics 2005; 1: 277-
4. Kenny LC, et al. Robust early pregnancy predictors of later pre-eclampsia using metabolomic biomarkers. Hypertension 2010; 56: 741-49.
5. Aitkinson KR, et al. An altered pattern of circulating apolipoprotein E3 isoforms is implicated in pre-eclampsia. J Lipid Research 2009; 50:71-80.
6. Turner E, et al. Plasma from women with pre-eclampsia has a low lipid and high ketone body content - A nuclear magnetic resonance study. Hypertension in Pregnancy 2007; 26:329-42.
7. Odibo AO, et al. First-trimester prediction of pre-eclampsia using metabolomics: a discovery phase study. Prenatal Diagnosis 2011; 31:990-94.
8. Bahado-Singh RO, et al. Metabolomics and first-trimester prediction of early-onset pre-eclampsia. Journal of Maternal-Fetal and Neonatal Medicine 2012;25:1840-47.
9. Horgan RP, et al. Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy. Journal of Proteome Research 2011; 3660-73.
10. Dani C, et al. Metabolic profile of term infants of gestational diabetic mothers. Journal of Maternal-Fetal and Neonatal Medicine 2013 doi: 10.3109/1476058.2013.823941.
11. Bittner V. Menopause and cardiovascular risk cause or consequence? J Am Coll Cardiol 2006;47:1984-86.
12. Report of the WHO Scientific Group. Research on the menopause in the 1990s. Geneva: World Health Organisation; 1996. Report No.: 886
13. Lawlor DA, Hardy R. A life course approach to metabolic and vascular function. Kuh D, Cooper R, Hardy R, Richards M, Ben-Shlomo Y, eds. A life course approach to healthy ageing. OUP; 2013.
14. Finish menopausal metabolomics study
B2166 - Association of birth circumstances experience of parental separation of young women with the risk of preterm delivery - 03/04/2014
Preterm birth is the leading cause of childhood disability and infant mortality in the developed world. The rate of preterm birth has been increasing in recent decades for reasons which are poorly understood. The rate of preterm birth is approximately 8% in the UK, 12% in the USA and 20% among African Americans.
The risk of preterm birth is highest for older mothers (greater than 35 years) and teenagers. There is a moderate association with marital status of parents in Europe and the USA, and a somewhat weaker association with poverty.
Witt et al (AJPH 2104) reports, from a US cohort, a high rate of preterm birth to teenage mothers and a four fold increased risk of preterm birth for teenage mothers who had experienced pre-conception stressful life events compared to those who had not.
There is a strong linear correlation for historical rates (up to 1972) of birth to unmarried parents with current rates of preterm birth in US states r greater than 0.65, p=0.000 (cdc data, correlation unpublished).
Goodman and Greaves (IFS 2010) report, from the MCS, a 4x and 3x relative risk of parental separation for cohabiting versus married parents when their children were 3 and 5 years old. Parental separation was a significant adverse influence on cognitive and social development in the children. There are also studies which report associations of family structure with rates of smoking and obesity. These are recognised risk factors for preterm birth.
There is empirical evidence that early life experiences influence the risk of preterm delivery for young mothers. Longitudinal studies could reveal how birth circumstances, including the marital status of parents, influence the likelihood of becoming a teenage mother and how they affect the risk of preterm birth in young mothers.
This information may carry the potential for clinical benefits, such as the identification and support of women with high risk pregnancies, and assist in the development of strategies for the prevention of both teenage pregnancy and preterm birth.
B2215 - Understanding participation and non-participation in HE for white working class and minority ethnic groups BIS - 27/03/2014
The principal aims of this project are:
1) To examine potential gaps in in the current understanding of why these groups are less likely to progress to HE and to test hypotheses using the ALSPAC dataset linked to NPD and HESA.
2) Undertake qualitative interviews with the groups of interest, in particular to establish what individuals felt were the barriers to higher education for them personally. For those who made the successful transition, we would like to understand the factors that contributed to their HE participation.
B2214 - Early life predictors of visual and refraction-related phenotypes in early adulthood - 27/03/2014
Aims
Our interest is in how early childhood exposures/behaviours influence the development of the visual system, its peak performance and markers of later sight-threatening disorders (such as glaucoma) and how these interact with genetic factors. Within this broad theme, we aim to address research questions framed by the following hypotheses.
B2213 - Parent-of-origin specific genome- and epigenome-wide analyses on fetal growth and postnatal outcome - 27/03/2014
Aim:
To identify genes important in fetal growth and postnatal outcome, using a parent-of-origin analysis model.
B2212 - Genetic variation and smoking - contribution to GSCAN GWAS Sequencing Consortium of Alcohol and Nicotine use - 27/03/2014
We will analyse the association between various smoking phenotypes in YPs and mothers and common genetic variation (GWAS, available for most YPs and mothers) and more rare genetic variation (based on GWAS data imputed to a novel imputation panel based on sequencing data, therefore available for most YPs and mothers, as well as on a subsample of the cohort with UK10K sequencing data).
YPs Analyses
Phenotypes to be analysed will include initiation, age at initiation, first response to tobacco, tobacco intake (as indexed by daily cigarette consumption), and level of nicotine dependence (based on the FTND questionnaire). Both cross-sectional measures and derived life-time consumption measures will be used. Where possible and appropriate, trajectories of use will be defined as part of an ongoing collaboration with Prof Matt Hickman and Dr Jon Heron.
Mothers Analyses
Phenotypes to be analysed will include initiation, age of initiation, tobacco intake (as indexed by daily cigarette consumption), level of nicotine dependence, and smoking cessation. Both cross-sectional measures and derived life-time consumption measures will be used.
A detailed analysis plan for the GWAS of individual studies to be included in the GSCAN collaboration is available online (http://gscan.sph.umich.edu/gwas/analysis_plan).
B2211 - Genetic variation and alcohol use - contribution to GSCAN GWAS Sequencing Consortium of Alcohol and Nicotine use - 27/03/2014
AIMS:
We will analyse the association between various dimensions of alcohol use in YPs and mothers and common genetic variation (GWAS, available for most YPs and mothers) and more rare genetic variation (based on GWAS data imputed to a novel imputation panel based on sequencing data, therefore available for most YPs and mothers, as well as on a subsample of the cohort with UK10K sequencing data).
B2209 - Maternal smoking in pregnancy in relation to offspring methylation and asthma - 27/03/2014
Aims:
We (Joubert et al. Environ Health Perspect. 2012;120:1425-31) and subsequently others have identified replicable methylation differences at birth in relation to maternal smoking using the Illumina 450K platform. Some of the same changes have been seen in adult smokers. It is not known whether these differences persist to later childhood, whether the persistence may differ across loci, or whether postnatal exposure might contribute to the persistence of these methylation changes. We propose to analyze ALSPAC data in the setting of meta-analysis across cohorts with data on maternal smoking during pregnancy and offspring Illumina 450K methylation and asthma phenotypes to address the following specific aims:
1. Do methylation differences at specific loci related to maternal smoking detected at birth persist to later childhood, taking into account postnatal exposure to smoking.
2. To examine the association between maternal smoking during pregnancy, assessed by plasma cotinine, and the development of asthma phenotypes in the child.
3. Investigate whether methylation differences at birth related to maternal smoking may be a biomarker of the risk of developing asthma phenotypes from exposure to maternal smoking during pregnancy.
B2204 - Early life stress age of puberty and reproductive behaviour - 20/03/2014
Objectives:
1. To provide a multi-faceted understanding of the causal variables underlying behaviour and the psychological correlates that form and mediate individual life history strategies, allowing a strong test of hypotheses of psychosocial acceleration in response to early adversity.
B2203 - Foetal testosterone 2D4D digit ratio and social cognition - 20/03/2014
Foetal testosterone plays a significant role in a wide range of sex-differences. In animal studies it has been found that foetal testosterone influences the development of the of the brain; the hypothalamus, limbic system, and neocortex (Arnold & Gorski, 1984; Breedlove, 1994; MacLusky & Naftolin, 1981). It has also been found to influence behaviours (Goy & McEwen, 1980) and cognitive abilities (Williams & Meck, 1991). Sex differences in behaviour and cognition are also apparent in humans (Baron-Cohen, 2003). Traditionally research in this area has focused on abilities of logic; spatial, mathematical, and verbal ability (Kimura, 1999). More recently investigations have looked at potential social sex differences. Geary (1998), suggested that women exceed men in particular aspects of socio-cognitive ability; non-verbal communication, language and theory of mind. Baron-Cohen (2002) proposed that women have a better ability to identify and understand another's state of mind, emotional state (empathy), and to respond appropriately.
Lower 2D:4D digit span ratio is a sexually dimorphic trait, thought to be indicative of higher testosterone exposure. On average males have a lower digit span ratio than females (Maning, 2002). Growth of the 4th digit, as promoted by testosterone, is thought to occur in a 'respective window' in utero and therefore 2D:4D ratio remains constant through out postnatal development. Subsequently 2D:4D has been deemed a useful biomarker for extent of prenatal testosterone exposure (Maning, 2002). There is an abundance of evidence in support of this view. For example, it has been found that women with congenital adrenal hyperplasia have more masculine span and males with the condition have smaller digit ratios than control males (Okten, Kalyoncu, & Yari?, 2002 ).
Whereas digit span ratio has been associated with numerous mental health disorders- Depression, Psychopathology, ADHD (Bailey & Hurd, 2005; Blanchard & Lyons, 2010; McFadden, Westhafer, Pasanen, Carlson, & Tucker, 2005), most frequently the literature has investigated links with social cognition and autism. Individuals with autism are thought to be subject to a hypermasculined brain, characterised by low empathising and high systemising traits. At the other end of the continuum the so-called feminised brain is characterised by high empathising and low systemising (Baron-Cohen, 2002). Deficits in social cognition and autistic traits have been found to be indirectly associated (via digit span ratio) with prenatal testosterone exposure (e.g. Honekopp, 2012). In support of these findings, more males have autism than females.
However, conclusions made by papers investigating digit pan ratio and social cognition are often based on small sample sizes (around 50 participants). Furthermore, a study by Voracek and Dressler (2006) which used a relatively large number of participants (N= 423), found a lack of correlation between 2D:4D and empathising, systemising and autistics traits, using measures developed by Baron-Cohen (2002). The purpose of this research is to better investigate whether a link between foetal testosterone and social cognition exists, specifically the ability to empathise. The aim of the study is, by using such a large data set, to overcome the experimental limitations to which previous studies may have succumb.
The exposure variable will be 2D:4D and outcomes variables will be social communication, non verbal information, theory of mind, friendships, and gender behaviour. If 2D:4D is indicative of in utero testosterone exposure, and this has organisational effects on brain development that are reflected in lateroutcomes, it is predicted that lower digit span ratio will be associated with poorer social communication, non- verbal information, theory of mind scores and friendships scores and more male typed gender behaviours.This hypotheses will be assessed using appropriate regression techniques.
B2202 - DNA methlyation and processing of facial emotion during 75 carbon dioxide anxiety challenge - 20/03/2014
Aims:
To investigate sources for individual variation in emotional face processing during state anxiety.
The majority of research has examined the association between trait anxiety and emotional processing. In contrast, the effects of state anxiety have been understudied. Our laboratory is experienced in the use of anxiogenic challenges that safely and transiently increase anxiety. This involves short (up to 20 minutes) inhalation of air that has higher levels of CO2 than normal air (7.5%). There is substantial individual variation in anxiety sensitivity and emotional processing, and in this study we would investigate whether effects differ on the basis of DNA methlyation patterns, which have recently been identifed as biological markers of early life stress. DNA methylation profiles have already been generated from the peripheral blood of approximately 1000 ALSPAC mothers and children as part of the Accessible Resource for Integrated Epigenomics Studies (ARIES).