Meta-analysis of total child/adolescent behaviour and emotional (combined) problem score, later followed by a meta-analyses of general psychopathology factor.

A) Relationship between glycemic index, dietary protein and myopia.

The Cordain theory [3] proposes that myopia occurs as a result of environmental conditions associated with modern civilisation, which came about after the Palaeolithic era. The prevalence of myopia is very low in hunter-gatherer populations compared to more "advanced" populations (less than 2% vs. greater than 20%) [1]. In Eskimos, increasing acculturation during the 1960's led to a marked increase in myopia prevalence [2]. The typical Palaeolithic diet is characterised as being high in protein, low in fat and low in carbohydrates, particularly low glycaemic index carbohydrates: which are slowly absorbed in the blood stream and produce a gradual and minimal rise in plasma glucose and insulin levels when compared to higher glycaemic foods . As well as being implicated in metabolic syndrome, the modern - lower protein/higher glycaemic index - diet has also been suggested as a potential risk factor for myopia [3].

Dietary protein has also been considered as a possible risk factor for myopia, because protein generally results in lower rises in both plasma glucose and insulin when compared to carbohydrate.

In a number of studies, Gardiner [4,5], indicated that myopic individuals consumed significantly lower amounts of animal protein than non-myopes. Further, in an intervention study (albeit a non-rigorous one) he was able to show that increasing the level of animal protein in the diets of myopic children slowed progression of their myopia when compared to a control group receiving no dietary modification [6].

B) Exploratory analysis: Dietary copper

Normal copper metabolism is essential to ocular tissue health and is associated with myopic refractive error development in some studies [7,8]. A recent study found that mutations in the SCO2 gene were associated with autosomal-dominant high-grade myopia. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Mutations of SCO2 were associated with a destabilisation of protein structures which in turn may result in modulation of oxidative toxicity-particularly in the retina, leading to retinal neuronal thinning. In addition, mutations can affect copper metabolism, which may result in an imbalance of copper enzymatic support activity and oxidative levels within eye tissues [9]. Proper copper metabolism is essential for cell differentiation, development, and maintenance. One study demonstrated the protective effect of copper supplements in individuals with myopia, restoration by capsule injection of copper compounds resulted in increased scleral copper concentration and improved scleral tissue elasticity with cessation of myopic refractive error development [10].

C) Exploratory analysis: Breastfeeding

Observational studies have suggested that breast-feeding benefits the visual development of infants, which has been attributed to the presence of DHA in breast milk but not most formula milks.

In a cross-sectional study of 797 children (ages 10-12 years) in Singapore, the prevalence of myopia was significantly lower in children who had been breastfed than in those who had not (62% vs. 69.1%; p=0.04). The duration of breastfeeding (three months or less versus more than three months) was not associated with myopia risk. However, since the incidence of myopia in children in Singapore is among the highest in the world, it is not clear whether these findings can be generalised to other populations [11].

Analyses of data from three large British birth cohorts showed that there were no differences in visual outcome in childhood or adolescence among those initially breastfed for greater than 1 mo compared with those formula fed. Rates of breastfeeding fell across successive cohorts considerably, but there was no evidence of a subsequent increase in adverse visual outcome in childhood, although, there was a small increase in adverse visual outcome in adolescence from 1946 to 1970. However, the latter did not take into consideration important confounding factors, especially the age at which vision was assessed. (12)

Overall Aim:

To calculate prevalence estimates of a range of self-reported key sexual health indicators and behavioural patterns as assessed in the ALSPAC cohort between the ages of 17 and 22 years of age in order to better understand the sexual health needs of young people in the Bristol area.

AIM:

This aim of this research proposal is to understand the impact that children's early physical and communication environments have on their developing speech and language skills. The findings will be of use to parents, health visitors, health promotion and public health, early years practitioners and educationalists with regard to which environments and behaviours are most helpful in promoting early speech and language development and which can have a deleterious effect. This is particularly important given recent changes in society which mean that children are being brought up in homes where there are numerous devices which can be used to occupy them rather than engage them in conversation. Moreover, other lifestyle factors could also be having an impact but to date have been subject to minimal investigation (e.g. central heating, forward facing buggies, eating together). Whilst there is much evidence on the importance of parent child interaction on the development of speech and language in young children, there has not been the opportunity to date to investigate how this interacts with these other factors relating to the physical environment.

The findings of this study will also be of interest to the government. A recent DfE report based on data from the original ALSPAC sample (Roulstone, Law, Rush, Clegg, Peters, 2011, DFE RR134) found that vocabulary scores at age 2 years old were associated with baseline scores on entry to primary school, which are themselves related to academic outcomes later on. Low academic outcomes and persistent speech and language impairment are both associated with poor social and economic outcomes and a greater cost to the nation. This study will aim to identify factors early on in the child's development, including data collected in the child's home, which could impact on vocabulary at age 2 and language skills and academic skills beyond.

In the course of collecting data on variables which impact on early speech and language development, normative data will be collected using tools which have been developed in the US and for which UK norms are not currently available. These data will be of help to health visitors and early years practitioners in the future as they will assist in the process of early identification of children at risk of speech and language impairment. Currently, children are not typically identified until age 2 at the earliest.

We would like to use the extensive ALSPAC resource to carry out investigations on common genetic influences and genetic overlaps between speech, language and communication related during childhood. These analyses will inform subsequent meta-GWAS within the framework of the GenLang Consortium

During this project we will study the development of non-cognitive skills across the life-course. Non-cognitive skills encompass a diverse range of skills including: motivation, perseverance, emotional intelligence, resilience, and self-regulation. We will investigate the genetic architecture of these skills, and particularly how these skills develop over time. ALSPAC has existing measures of non-cognitive skills measured repeatedly across childhood. Further measures are being collected in the Focus @24/25 YP clinic as part of Marcus Munafo's research. During this project we would like to collect further measures of non-cognitive skills via a questionnaire during 2016 or 2017. We will collect comparable measures to other major cohort studies, including the English Longitudinal Study of Aging and The Health and Retirement Study in the US, which will enable the data to be used in a large GWAS consortia. As part of the project comparable data will be collected in TEDS.

We will perform a MR study to estimate the effect of age at menarche on parameters of lung function indicative of both restriction (FVC) and obstruction (FEV1/FVC). For this we would like to use ALSPAC lung function data from 16-year old women.

The aim of this study is to identify differential methylation in cord blood that is associated with AMH levels in female and male adolescents (separately) 15 years of age.

Genome-wide association analysis of 2D:4D finger ratio