Debbie Lawlor

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),...

More time outdoors is associated with a lesser risk of myopia, but the underlying mechanism is unclear. We tested the hypothesis that 25-hydroxyvitamin D (vitamin D) mediates the protective effects of time outdoors against myopia. We analyzed data for children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) population-based birth cohort: noncycloplegic autorefraction at age 7 to 15 years; maternal report of time outdoors at age 8 years and serum vitamin D2 and D3 at age 10 years. A survival analysis hazard ratio (HR) for incident myopia was calculated for children spending a high- versus low-time outdoors, before and after controlling for vitamin D level (N = 3677). Total vitamin D and D3, but not D2, levels were higher in children who spent more time outdoors (mean [95% confidence interval (CI)] vitamin D in nmol/L: Total, 60.0 [59.4-60.6] vs. 56.9 [55.0-58.8], P = 0.001; D3, 55.4 [54.9-56.0] vs. 53.0 [51.3-54.9], P = 0.014; D2, 5.7 [5.5-5.8] vs. 5.4 [...

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 an...

This study explores associations of IQ at age 14 with adult symptoms of suicidal thoughts and attempts at age 21. Analysis was based on the Mater University Study of Pregnancy and its outcomes, an Australian prospective birth cohort study started in Brisbane Australia in 1981. We assessed associations with suicide thoughts, plans, and attempts. We used two measures of IQ: the Raven's Standard Progressive Matrices and the Wide Range Achievement Test. In multivariable analyses, there was an inverse association between Raven's IQ and suicide thoughts, plans, and attempts, but no strong evidence of an association between the WRAT3 and the three suicidal items. Specific aspects of intelligence may be associated with suicidal thoughts, plans, and attempts.

Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0-3 months, 3 months-1 y, 1-3 y, 3-7 y, and 7-10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1-3 y, 3-7 y, and 7-10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness.

To estimate the impact family factors shared by siblings has on the association between length of education and cause-specific mortality in adulthood. The study population (n = 871 367) was all Norwegians born 1940-59 having one or more sibling within the cohort and alive in 1990. Length of education was obtained in 1990. Follow-up of deaths was from 1991 to 2008 when participants were aged 32-68 years. Sixty-five per cent of participants had one or more siblings who had completed a different number of years of formal education. A one-category difference in education was associated with a 30% increase in the hazard rate of death by all causes among men in the cohort analysis and 23% in within siblings analysis, and in women, increases were 22% and 14%, respectively. For cardiovascular disease, increases were 36% and 25% in men and 51% and 36% in women. For lung cancer, they were 48% and 29% in men and 53% and 22% in women. External causes and alcohol-related causes in men were generally similar in both analyses. This study suggests that at least some of the educational inequalities in all-cause, cardiovascular disease and lung cancer, external and alcohol-related mortality are explained by factors shared by siblings.

We conducted a family-based study to explore mechanisms underlying the associations of birth weight and gestational age with systolic blood pressure measured at 17 to 19 years of age. A record linkage study of 386,485 singleton-born men from 331,089 families was undertaken. Birth weight was inversely associated with systolic blood pressure within siblings, with a mean difference (adjusted for age at examination, examination center, and year of examination) within siblings per 1-SD difference in birth weight of -0.21 mm Hg (95% CI, -0.33 to -0.08) and between nonsiblings of -0.12 (95% CI, -0.16 to -0.08). Gestational age was inversely associated with systolic blood pressure within siblings (-0.18 mm Hg; 95% CI, -0.25 to -0.11, per week of gestational age) and between nonsiblings (-0.26 mm Hg; 95% CI, -0.29 to -0.24). Adjustment for socioeconomic position and maternal characteristics did not alter these within- or between-family associations. Furthermore, the associations were not affected by adjustment for paternal height, body mass index, or systolic blood pressure. Our present findings suggest that the inverse associations of birth weight and gestational age with systolic blood pressure are not explained by confounding resulting from family socioeconomic position or other factors that are shared by siblings. Variations in maternal metabolic or vascular health during pregnancy or placental implantation and function may explain these associations.