Born in Bradford
Ontology highlight
ABSTRACT:
PROVIDER: EGAO00000000710 | EGA |
REPOSITORIES: EGA
Publications
Health and population effects of rare gene knockouts in adult humans with related parents.
Narasimhan Vagheesh M VM Hunt Karen A KA Mason Dan D Baker Christopher L CL Karczewski Konrad J KJ Karczewski Konrad J KJ Barnes Michael R MR Barnett Anthony H AH Bates Chris C Bellary Srikanth S Bockett Nicholas A NA Giorda Kristina K Griffiths Christopher J CJ Hemingway Harry H Jia Zhilong Z Kelly M Ann MA Khawaja Hajrah A HA Lek Monkol M McCarthy Shane S McEachan Rosie R O'Donnell-Luria Anne A Paigen Kenneth K Parisinos Constantinos A CA Sheridan Eamonn E Southgate Laura L Tee Louise L Thomas Mark M Xue Yali Y Schnall-Levin Michael M Petkov Petko M PM Tyler-Smith Chris C Maher Eamonn R ER Trembath Richard C RC MacArthur Daniel G DG Wright John J Durbin Richard R van Heel David A DA
Science (New York, N.Y.) 20160303 6284
Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were link ...[more]
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Project description:BackgroundBradford, one of the most deprived cities in the United Kingdom, has a wide range of public health problems associated with socioeconomic deprivation, including an infant mortality rate almost double that for England and Wales. Infant mortality is highest for babies of Pakistani origin, who comprise almost half the babies born in Bradford. The Born in Bradford cohort study aims to examine environmental, psychological and genetic factors that impact on health and development perinatally, during childhood and subsequent adult life, and those that influence their parents' health and wellbeing. This protocol outlines methods for the recruitment phase of the study.MethodsMost Bradford women attend for antenatal care and give birth at the Bradford Royal Infirmary, which has approximately 5,800 births per year. Women are eligible for recruitment if they plan to give birth here. Babies born from March 2007 are eligible to participate, recruitment is planned to continue until 2010. Fathers of babies recruited are invited to participate. Women are usually recruited when they attend for a routine oral glucose tolerance test at 26-28 weeks gestation. Recruitment of babies is at birth. Fathers are recruited whenever possible during the antenatal period, or soon after the birth. The aim is to recruit 10,000 women, their babies, and the babies' fathers. At recruitment women have blood samples taken, are interviewed to complete a semi-structured questionnaire, weighed, and have height, arm circumference and triceps skinfold measured. Umbilical cord blood is collected at birth. Within two weeks of birth babies have their head, arm and abdominal circumference measured, along with subscapular and triceps skinfold thickness. Fathers self-complete a questionnaire at recruitment, have height and weight measured, and provide a saliva sample. Participants are allocated a unique study number. NHS numbers will be used to facilitate record linkage and access to routine data. A wide range of hospital and community sources is being accessed to provide data for the women and children. Data are checked for accuracy and consistency.ConclusionBorn in Bradford will increase understanding of the factors that contribute to health and wellbeing, and identify factors that influence differences in them between people of Pakistani and European origin.
| S-EPMC2562385 | biostudies-literature
Project description:BackgroundBorn in Bradford (BiB) is a prospective multi-ethnic pregnancy and birth cohort study that was established to examine determinants of health and development during childhood and, subsequently, adult life in a deprived multi-ethnic population in the north of England. Between 2007 and 2010, the BiB cohort recruited 12,453 women who experienced 13,776 pregnancies and 13,858 births, along with 3353 of their partners. Forty five percent of the cohort are of Pakistani origin. Now that children are at primary school, the first full follow-up of the cohort is taking place. The aims of the follow-up are to investigate the determinants of children's pre-pubertal health and development, including through understanding parents' health and wellbeing, and to obtain data on exposures in childhood that might influence future health.MethodsWe are employing a multi-method approach across three data collection arms (community-based family visits, school based physical assessment, and whole classroom cognitive, motor function and wellbeing measures) to follow-up over 9000 BiB children aged 7-11 years and their families between 2017 and 2021. We are collecting detailed parent and child questionnaires, cognitive and sensorimotor assessments, blood pressure, anthropometry and blood samples from parents and children. Dual x-ray absorptiometry body scans, accelerometry and urine samples are collected on subsamples. Informed consent is collected for continued routine data linkage to health, social care and education records. A range of engagement activities are being used to raise the profile of BiB and to disseminate findings.DiscussionOur multi-method approach to recruitment and assessment provides an efficient method of collecting rich data on all family members. Data collected will enhance BiB as a resource for the international research community to study the interplay between ethnicity, socioeconomic circumstances and biology in relation to cardiometabolic health, mental health, education, cognitive and sensorimotor development and wellbeing.
| S-EPMC6626420 | biostudies-literature
Project description:Data Access Committee EGAC00001003494
| EGAC00001003494 | EGA
Project description:Background: Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was mediated by foetal kidney size. Methods: Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. Results: 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m 2 (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m 2, 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. Conclusions: There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty.
| S-EPMC10233317 | biostudies-literature
Project description:OBJECTIVES:Explore associations between maternal and neonatal outcomes and maternal age, with particular reference to adolescent women. DESIGN:Population-based cohort study. SETTING:Maternity department of a large hospital in Northern England. PARTICIPANTS:Primiparous women delivering a singleton at Bradford Royal Infirmary between March 2007 and December 2010 aged ?19 years (n=640) or 20-34 years (n=3951). Subgroup analysis was performed using women aged ?16 years (n=68). Women aged 20-34 years were used as the reference group. PRIMARY OUTCOME MEASURES:Maternal and neonatal outcomes. RESULTS:The odds of extremely low birth weight (<1000?g) were significantly higher in the adolescent group (?19 years) compared with the reference group (adjusted OR (aOR) 4.13, 95% CI 1.41 to 12.11). The odds of very (<32 weeks) and extremely (<28 weeks) preterm delivery were also higher in the adolescent group (aOR 2.12, 95% CI 1.06 to 4.25 and aOR 5.06, 95% CI 1.23 to 20.78, respectively).Women in the adolescent group had lower odds of gestational diabetes (aOR 0.35, 95% CI 0.20 to 0.62), caesarean delivery (aOR 0.53, 95% CI 0.42 to 0.67 and instrumental delivery (aOR 0.53, 95% CI 0.41 to 0.67). CONCLUSIONS:This study identifies important differences in maternal and neonatal outcomes between women by age group. These findings could help in identifying at-risk groups for additional support and tailored interventions to minimise the risk of adverse outcomes for these vulnerable groups. Further work is needed to identify the causal mechanisms linking age with outcomes in adolescent women where significant gaps in the literature exist.
| S-EPMC5857698 | biostudies-literature
Project description:The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples.
| EGAS00001000462 | EGA
Project description:Prenatal socioeconomic disadvantage (SD) has been linked to DNA methylation (DNAm) in adulthood, but whether such epigenetic alterations are present at birth remains unclear. We carried out an epigenome-wide analysis of the association between several measures of individual- and area-level prenatal SD and DNAm assessed in neonatal cord blood via the Infinium EpicBeadChip among offspring born to mothers of White British (N = 455) and Pakistani (N = 493) origin in the Born in Bradford Study. Models were adjusted for mother's age, ethnicity, and education level as well as cell-type fractions and then for maternal health behaviours and neonate characteristics, and last, stratified by mother's ethnicity. P-values were corrected for multiple testing and a permutation-based approach was used to account for small cell sizes. Among all children, housing tenure (owning versus renting) as well as father's occupation (manual versus non-manual) were each associated with DNAm of one CpG site and index of multiple deprivation (IMD) was associated with DNAm of 11 CpG sites. Among children born to White British mothers, father's occupation (student or unemployed versus non-manual) was associated with DNAm of 1 CpG site and IMD with DNAm of 3 CpG sites. Among children born to Pakistani mothers, IMD was associated with DNAm of 1 CpG site. Associations were largely unchanged after further adjustment for maternal health behaviours or neonate characteristics and remained statistically significant. Our findings suggest that individual- and area-level prenatal SD may shape alterations to the neonatal epigenome, but associations vary across ethnic groups.
| S-EPMC9665119 | biostudies-literature
Project description:Rates of advanced chronic kidney disease and renal replacement therapy are higher in South Asian than in white British populations. Low birth weight is also more frequent in South Asian populations and has been associated with increased risks of kidney disease, perhaps due to a reduced nephron endowment.Using ultrasound scans at 34 weeks of gestation, we measured fetal kidney dimensions (transverse and anteroposterior diameters, length and circumference) and derived volume in a random sample of 872 white British and 715 South Asian participants in the Born in Bradford cohort study. Kidney measurements were compared between ethnic groups.Birth weight for gestational age at 40 weeks was 200 g less in South Asian babies compared with white British babies. The mean kidney volume for gestational age was 16% lower in South Asian than in white British babies [8.79 versus 10.45 cm(3), difference 1.66 cm(3) (95% confidence interval 1.40-1.93, P < 0.001)]. The difference was robust after adjustment for maternal age, socio-economic factors, marital status, body mass index, smoking and alcohol use in pregnancy, parity, baby's gender and birth weight for gestational age [adjusted difference 1.38 cm(3) (0.97-1.84), P < 0.001]. There were smaller reductions in other fetal measures.South Asian babies have smaller kidneys compared with white British babies, even after adjusting for potential confounders including birth weight. This finding may contribute to increased risks of adult kidney disease in South Asian populations.
| S-EPMC6071385 | biostudies-other
Project description:BackgroundFoetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7-11 years.MethodsFoetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm3) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7-11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders.ResultsKidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure.ConclusionFoetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required.
| S-EPMC9945391 | biostudies-literature
Project description:To examine independent associations of sleep duration with total and abdominal adiposity, and the bidirectionality of these associations, in a young biethnic sample of children from a disadvantaged location. Child sleep duration (h/day) was parent-reported by questionnaire and indices of total (body weight, body mass index, percent body fat (%BF), sum of skinfolds) and abdominal adiposity (waist circumference) were measured using standard anthropometric procedures at approximately 12, 18, 24, and 36 months of age in 1,338 children (58% South Asian; 42% White). Mixed effects models were used to quantify independent associations (expressed as standardised β-coefficients (95% confidence interval (CI)) of sleep duration with adiposity indices using data from all four time-points. Factors considered for adjustment in models included basic demographics, pregnancy and birth characteristics, and lifestyle behaviours. With the exception of the sum of skinfolds, sleep duration was inversely and independently associated with indices of total and abdominal adiposity in South Asian children. For example, one standard deviation (SD) higher sleep duration was associated with reduced %BF by -0.029 (95% CI: -0.053, -0.0043) SDs. Higher adiposity was also independently associated with shorter sleep duration in South Asian children (for example, %BF: β = -0.10 (-0.16, -0.028) SDs). There were no significant associations in White children. Associations between sleep duration and adiposity are bidirectional and independent among South Asian children from a disadvantaged location. The results highlight the importance of considering adiposity as both a determinant of decreased sleep and a potential consequence.
| S-EPMC5804981 | biostudies-literature