In Western countries, there are no cohorts of childhood refraction data large enough to provide the statistical power to detect subtle genetic effects (e.g. QTL controlling less than 5% of the variation in the trait phenotype). This study will provide complementary information to a moderately sized study (1400 children) in Asia, in which refraction data has been collected, and selected SNP genotyping is planned. This work will also provide preliminary data to inform a future genomewide association studies for refractive error in this cohort.

We will link the above variables to the data on atopic outcomes and confounders (and PSAI score) which we already have, and carry out appropriate multivariate analyses in boys and girls separately. We will examine relations of digit ratio to the other variables above, and to testosterone levels in pregnancy in the subset with these data. We will stratify by maternal atopic disease and parity (especially number of older brothers which has been linked to digit ratio and to atopy), and stratify the handedness analyses by family history of atypical handedness. We could also relate maternal handedness to atopic disease in the mothers. If we confirm novel associations with digit ratio we will write these results up first.

(No outline received).

No outline received

Background: It has been clear for some years now: overweight and obesity are a major problem for public health in developed and developing countries [WHO World Health Report 2002]. Changes in both physical activity levels and nutrition have contributed to this problem. These changes are partly due to changes in economic standards, culture and social norms, as well as to changes in our environment. Cars, computers, escalators, and remote controls have all made their entry in our lives in the past century. The discussion about whether and to what extent we can compensate and manage these changes, and what impact this would have on overweight and obesity prevalence, is ongoing. Changes in our environment have not been limited to the places where we live and work.

Because expectant mothers today are different from those who lived a century ago (for example they are generally fatter and less physically active during pregnancy [Kramer 2002]), the intrauterine environment has also changed over time. These changes in the intrauterine environment are reflected in the fact that birth weight increased between 1978-1996, with a corresponding drop in small-for-gestational age (SGA) babies and increase in large-for-gestational-age (LGA) babies [Kramer 2002].

The importance of birth weight for the development of chronic disease later in life was first recognised by Barker [1995]. His hypothesis was that SGA babies were at increased risk for cardiovascular disease later in life. Hence, the attention was at first predominantly on SGA babies. However, more recently, LGA babies have been found to be at risk as well. In addition to the fact that giving birth to an LGA baby is a risk for complications during childbirth [e.g. Oral 2001], these babies have disproportionately more fat in childhood. Hammami et al. [2001] have shown that body weight and length are the dominant predictors of body composition in LGA and appropriate-for-gestational age (AGA) neonates. They also found that LGA neonates have significantly higher proportions of total body fat and bone mineral content, but lower lean body mass as a percent of body weight. In contrast, Hediger et al. did not find a surfeit of fatness in infants born LGA within the first years after birth [Hediger 1998], but found an increase in fatness at the triceps and subscapular sites at 3 years of age [Hediger 1999]. Rogers et al. [2006] found that an increased relative weight-for-height at birth was associated with increased fat mass. Based on these findings, it seems that prevention of LGA births could be important in the prevention of overweight and obesity and related health problems later in life.

Several researchers have shown that increased maternal body mass index (BMI) is partly responsible for the rise in proportion of LGA births over time [Kramer 2002; Surkan 2004], and it is consistently related to the risk of LGA births [Orskou 2003; Schaefer- Graf 2002 & 2003]. Other lifestyle factors reducing the risk of LGA births are smoking and caffeine intake during pregnancy [Orskou 2003]. Since levels of smoking are falling in most Western countries, this may also contribute to a higher number of LGA babies [Kramer 2002].

Maternal glucose tolerance is another strong determinant of LGA birth. Women with gestational diabetes (GDM) have a strongly increased risk of giving birth to a LGA baby [Schaefer-Graf 2002 & 2003]. Not only is their risk of an LGA birth higher, the consequences of LGA are more pronounced in babies whose mothers had GDM. Evidence suggests that the increase in fat mass in LGA babies [Hediger 1998; Hammami 2001] is larger in LGA babies following GDM pregnancies, than in LGA babies whose mothers had normal glucose tolerance [Hammami 2001; Vohr 1997 & 1999]. Moreover, Vohr et al. have shown that fat mass in LGA children whose mothers had GDM was higher than in LGA babies from 'control' women, even at 7 years of age [Vohr 1999]. In addition to this increased adiposity, they also found that LGA babies of GDM mothers also had higher blood pressure and higher levels of serum glucose at 4-7 years of age. Adverse effects of LGA births also include a higher risk for the development of insulin intolerance and obesity during childhood [Strauss 1997].

In relation to maternal physical activity, Alderman et al. [1998] have shown that moderate or vigorous physical activity for two hours per week or more in any month of pregnancy is associated with decreased risk of LGA birth, but has no significant effect on risk of SGA birth or length of gestation. They postulate that this effect may be due to beneficial effects on glucose tolerance. If so, physical activity may not only reduce the risk of LGA birth, but may also reduce the associated increase in adiposity. This effect may be more pronounced in babies born to GDM mothers. However, the role of physical activity during pregnancy on fat distribution in infancy has not been studied to date. Given the strong influence of physical activity on glucose metabolism, this relationship is very plausible.

No outline received

Purpose

There is growing evidence of the role of specific dietary factors in cancer prevention.

In a large, contemporary group of young people (the ALSPAC cohort), now at the

cusp of adulthood, this study will identify a dietary pattern characterised by these

cancer-protective components and study the antecedent determinants of these

eating habits. This will include the role of socio-economic status, parental attitudes

and behaviours and specific genetic traits, primarily relating to taste perception. It

will also examine the extent of tracking of dietary habits throughout childhood and

adolescence to adulthood. Together this data will inform public health strategies to

encourage the early adoption of a cancer-protective diet.

No outline received

In adult women asthma severity has been associated with phase in menstrual cycle1, reported early menarche2 and pregnancy3. Incident asthma has been associated with the use of hormone replacement therapy4 and with the use of the oral contraceptive (abstract only) with effects being more marked in lean women . These observations suggest that exposure to female sex hormones is important in asthma but the hormonal profile that would explain these associations is far from clear5. Studying children, particularly but not exclusively girls, through puberty may improve our understanding of the disease.

There are few large cohort studies with detailed information on asthma phenotype (eg;symptoms, atopic status and lung function), pubertal stage and other relevant physiological (eg: waist hip ratio; fasting blood sugar) and lifestyle/environmental factors (eg exercise). To date only the Tucson cohort has examined in depth the association of asthma with puberty but these analyses are insufficiently powered to fully disentangle the effects of obesity, age of puberty and differences between boys and girls. In the 1200 children studied analyses have suggested that there is a strong association of new asthma onset6 with increase in BMI - particularly in girls with early menarche - and that there is greater persistence of asthma symptoms through adolescence in those who are obese and in those with early puberty -associations observed in both boys and girls7 and which are independent of each other.

While it is widely thought that the association of asthma with early puberty may reflect a direct effect of hormones on asthma, an alternative hypotheses is that it reflects an underlying association of asthma with the metabolic syndrome. Epidemiological evidence for this is an association of asthma and some atopic markers with menstrual symptoms suggestive of polycystic ovarian syndrome (a feature of metabolic syndrome) 8 and studies suggesting an association of markers of insulin resistance with abnormal lung function9;10

The proposed collaboration would aim to:

1) Describe gender differences in asthma onset and asthma persistence from ages 8 to 15 years

2) Assess the association of age of puberty with asthma onset, asthma persistence, atopy and lung function

3) Develop from these testable hypotheses to explain observed associations. This would lead to a grant application for personnel and possibly further physiological/serological measures (including questionnaire based/physiological measures for the next follow-up). The application would most likely be to Asthma UK where asthma in adolescence has been identified as a priority area for research.