Jean Golding

Exposure to high levels of environmental lead, or biomarker evidence of high body lead content, are associated with anaemia, developmental and neurological deficits in children, and increased mortality in adults. Adverse effects of lead still occur despite substantial reduction in environmental exposure. There is genetic variation between individuals in blood lead concentration but the polymorphisms contributing to this have not been defined. We measured blood or erythrocyte lead content, and carried out genome-wide association analysis, on population-based cohorts of adult volunteers from Australia and the UK (N=5433). Samples from Australia were collected in two studies, in 1993-96 and 2002-05, and from the UK in 1991-92. One locus, at ALAD on chromosome 9, showed consistent association with blood lead across countries and evidence for multiple independent allelic effects. The most significant SNP, rs1805313 (p=3.91 x 10(-14) for lead concentration in a meta-analysis of all data),...

Transgenerational effects of different environmental exposures are of major interest, with rodent experiments focusing on epigenetic mechanisms. Previously, we have shown that if the study mother is a non-smoker, there is increased mean birth weight, length and body mass index (BMI) in her sons if she herself had been exposed prenatally to her mother's smoking. The aim of this study was to determine whether the prenatal smoke exposure of either parent influenced the growth of the fetus of a smoking woman, and whether any effects were dependent on the fetal sex. Population-based prebirth cohort study. Avon Longitudinal Study of Parents and Children. Participants were residents of a geographic area with expected date of delivery between April 1991 and December 1992. Among pregnancies of mothers who smoked during pregnancy, data were available concerning maternal and paternal prenatal exposures to their own mother smoking for 3502 and 2354, respectively. Birth weight, length, BMI a...

Previously, in the Avon Longitudinal Study of Parents and Children (ALSPAC), we have shown different sex-specific birth anthropometric measurements contingent upon whether or not prenatal smoking was undertaken by paternal grandmother (PGM±), maternal grandmother (MGM±), and the study mother (M±). The findings raised the question as to whether there were long-term associations on the growth of the study children over time. Measures of weight, height, body mass index, waist circumference, lean mass, and fat mass of children in the ALSPAC study from 7 to 17 years of age were used. We compared growth in four categories at each age: PGM+M- with PGM-M-; MGM+M- with MGM-M-; PGM+M+ with PGM-M+; MGM+M+ with MGM-M+; and adjusted for housing tenure, maternal education, parity, and paternal smoking at the start of the study pregnancy. We found that if the PGM had, but the study mother had not, smoked in pregnancy, the girls were taller and both genders had greater bone and lean mass. However, ...

Children confront the formidable task of assimilating information in the environment and accommodating their cognitive structures to that information. Developmental science is concerned equally with two distinctive features of these processes: children's group mean level of performance through time and the standing of individual children through time. Prevailing opinion since the inception of the mental-measurement movement has been that individual development is unstable-that individual children change unpredictably in their abilities. We report results of a large-scale controlled, multivariate, prospective, microgenetic, 4-year longitudinal study that reveals a statistically significant cascade of species-typical cognitive abilities from infancy to childhood. Infancy is a recognizable starting point of life; we find that to a small but significant degree, infancy also represents a setting point in the life of the individual.

The objective of this study was to examine differences in intellectual capacities between children with and without soiling, daytime wetting, and bed-wetting. This study was based on a population of >6000 children (age range: 7 years 6 months to 9 years 3 months; median: 7 years 6 months) from the United Kingdom-based Avon Longitudinal Study of Parents and Children. Data on wetting and soiling were obtained from a questionnaire completed by parents. The Wechsler Intelligence Scale for Children-Third Edition was administered at a research clinic. Bed-wetting was associated with lower Wechsler Intelligence Scale for Children-Third Edition IQ scores compared with control subjects, particularly performance IQ. This difference remained after exclusion of children with an IQ of <70 and adjustment for gender, stressful life events, and sociodemographic background. There were fewer differences in IQ scores between children with and without soiling or daytime wetting. Co-occurring wetting and soiling were associated with lower IQ scores than isolated soiling, daytime wetting, or bed-wetting, but this was mostly attributable to an overrepresentation of children with an IQ of <70 in the co-occurrence group. It is hypothesized that the differences in intellectual capacities between children with and without bed-wetting are associated with maturational deficits of the central nervous system. There was less evidence for differences in intellectual capacities between children with and without soiling and daytime wetting. The central nervous system is involved to a lesser extent in soiling and daytime wetting, because peripheral influences from the bladder and gut play a greater role.

Studying children in different types of families-intact, single-mother, and stepparent families-affords opportunities for testing models of gene-environment processes, based on estimates of sibling similarity among full-siblings and half-siblings. We used a stepfamily quantitative genetic design to estimate genetic and environmental sources of variance in children's behavior problems and prosocial behaviors, as well as negativity in their relationships with their mothers

Despite interest in the idea that transgenerational effects of adverse exposures might contribute to population health trends, there are few human data. This non-genetic inheritance is all the more remarkable when transmission is down the male-line as reported in a historical Swedish study, where the paternal grandfather's food supply in mid childhood was associated with the mortality rate in his grandsons. Using the Avon Longitudinal Study of Parents and Children's questionnaire data on smoking and smoking onset from 9886 fathers, we examined the growth of their children from 7-17 years. Adjusting for potential confounders, we assessed associations between body mass index (BMI), waist circumference, total fat mass and lean mass with the age at which the father had started smoking regularly. Of 5376 fathers who reported having ever smoked, 166 reported regular smoking <11 years of age. Before adjustment, those offspring whose fathers started smoking <11 years had the highest mean BMIs at each age tested. The adjusted mean differences in BMI, waist circumference and total fat mass in those sons whose fathers started smoking <11 years, compared with all other sons, increased with age, being significantly greater from 13 years onwards. There were no significant BMI associations in daughters, but they showed a reduction in total lean mass. Our results highlight the importance of the developmental timing of the paternal exposure as well as gender differences in offspring outcomes. Smoking by boys in mid childhood may contribute to obesity in adolescent boys of the next generation.