Project description:The National Child Development Study (NCDS) - also known as the 1958 British Birth Cohort (1958BC) - is a continuing, multi-disciplinary longitudinal study which takes as its subjects all the people born in one week in March 1958 in England, Scotland and Wales. The resource is used widely for research in genetic and genomic epidemiology - in particular as a platform for genetic association studies. Data are released under various Data Access Agreements. (1) Data users requesting genotype data only should apply to the Wellcome Trust Case Control consortium Data Access Committee (EGAC00000000001). (2) Those requesting phenotype data only should apply to the (ESRC) UK Data Archive (for more information please email to help@esds.ac.uk). (3) Those requesting linked genotype and phenotype data should apply to the Access Committee for the CLS Cohorts (for more information email to cohort1958@le.ac.uk).
Project description:T1DGC genome-wide case-control association study for Type 1 Diabetes (T1D) using the 1958 British Birth Cohort as controls. The cases for this study are made available from the NCBI dbGAP.
Project description:The aim is to examine the association of lifecourse socioeconomic position (SEP) on circulating levels of D-dimer. Data from the 1958 British birth cohort were used, social class was determined at three stages of respondents' life: at birth, at 23 and at 42 years. A cumulative indicator score of SEP (CIS) was calculated ranging from 0 (always in the highest social class) to 9 (always in the lowest social class). In men and women, associations were observed between CIS and D-dimer (P<0.05). Thus, the respondents in more disadvantaged social classes had elevated levels of D-dimer compared to respondents in less disadvantaged social class. In multivariate analyses, the association of disadvantaged social position with D-dimer was largely explained by fibrinogen, C-reactive protein and von Willebrand Factor in women, and additionally by smoking, alcohol consumption and physical activity in men. Socioeconomic circumstances across the lifecourse at various stages also contribute independently to raised levels of D-dimer in middle age in women only. Risk exposure related to SEP accumulates across life and contributes to raised levels of D-dimer. The association of haemostatic markers and social differences in health may be mediated by inflammatory and other markers.
Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates.
Project description:Studies that have examined associations between adverse childhood experiences (ACEs) and cardiometabolic biomarkers in adulthood are limited as they mainly focus on childhood maltreatment. This study aimed to examine the association between a range of prospectively and retrospectively reported ACEs and cardiometabolic biomarkers in mid-adulthood. Multiply-imputed data on 8511 participants from the National Child Development Study (1958 British birth cohort) were used. ACEs were prospectively reported at ages 7, 11 and 16, and retrospectively reported at age 33/44/45. Cardiometabolic outcomes assessed at age 44/45 included glycated haemoglobin (HbA1c), cholesterol (total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)), triglycerides, blood pressure (systolic and diastolic), body mass index, waist circumference and metabolic syndrome. Parental separation/divorce, physical neglect, emotional neglect and psychological abuse were associated with lower HDL cholesterol. Parental offending and physical neglect were associated with higher triglyceride concentrations. Parental offending was also associated with increased HbA1c. Exposure to 2+ (vs. 0) prospective ACEs was associated with lower HDL cholesterol. All these associations were after adjustment for sex and multiple early life factors. To conclude, several individual ACEs are associated with poorer cardiometabolic risk factor profiles in mid-adulthood. Furthermore, exposure to two or more prospective ACEs is associated with lower HDL cholesterol concentrations in mid-adulthood. Highlights • Parental separation/divorce in childhood is associated with lower high-density lipoprotein cholesterol in mid-adulthood.• Physical neglect in childhood is associated with poorer lipid profiles in mid-adulthood.• Psychological abuse in childhood is associated with lower high-density lipoprotein cholesterol in mid-adulthood.• Parental offending in childhood is associated with higher triglycerides and glycated haemoglobin in mid-adulthood.
Project description:ObjectiveTo determine any association of amblyopia with diverse educational, health, and social outcomes in order to inform current debate about population screening for this condition.Design, setting, and participantsComparison of 8432 people with normal vision in each eye with 429 (4.8%) people with amblyopia (childhood unilateral reduced acuity when tested with correction and unaccounted for by eye disease) from the 1958 British birth cohort, with respect to subsequent health and social functioning.ResultsNo functionally or clinically significant differences existed between people with and without amblyopia in educational outcomes, behavioural difficulties or social maladjustment, participation in social activities, unintended injuries (school, workplace, or road traffic accidents as driver), general or mental health and mortality, paid employment, or occupation based social class trajectories.ConclusionsIt may be difficult to distinguish, at population level, between the lives of people with amblyopia and those without, in terms of several important outcomes. A pressing need exists for further concerted research on what it means to have amblyopia and, specifically, how this varies with severity and how it changes with treatment, so that screening programmes can best serve those who have the most to gain from early identification.
Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates. 36 Umbilical cord blood samples were collected in EDTA tubes soon after placental delivery. Blood samples were centrifuged at 3,000 RPM to separate plasma, and buffy coats were aliquoted and stored at -80oC. DNA was extracted using the DNeasy Kit (Qiagen). DNA methylation was interrogated for each sample using the HumanMethylation450 BeadChip (Illumina).
Project description:To analyse whether Adverse Childhood Experiences (ACE) are associated with an increased risk of cancer.The National child development study (NCDS) is a prospective birth cohort study with data collected over 50 years. The NCDS included all live births during one week in 1958 (n=18558) in Great Britain. Self-reported cancer incidence was based on 444 participants reporting having had cancer at some point and 5694 reporting never having cancer. ACE was measured using reports of: 1) child in care, 2) physical neglect, 3) child's or family's contact with the prison service, 4) parental separation due to divorce, death or other, 5) family experience of mental illness & 6) family experience of substance abuse. The resulting variable had three categories, no ACEs/ one ACE/ 2+ACEs and was used to test for a relationship with cancer. Information on socioeconomic characteristics, pregnancy and birth were extracted as potential confounders. Information on adult health behaviours, socioeconomic environment, psychological state and age at first pregnancy were added to the models. Multivariate models were run using multiply-imputed data to account for missing data in the cohort.The odds of having a cancer before 50 y among women increased twofold for those who had 2+ ACEs versus those with no ACEs, after adjusting for adult factors and early life confounders (OR: 2.1, 95% CI: 1.42-3.21, p<0.001).These findings suggest that cancer risk may be influenced by exposure to stressful conditions and events early on in life. This is potentially important in furthering our understanding of cancer aetiology, and consequently in redirecting scientific research and developing appropriate prevention policies.