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]
Similar Datasets
Project description:Bradford, 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.Most 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.Born 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: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: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:Study objectivesTo 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.MethodsChild 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.ResultsWith 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.ConclusionsAssociations 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
Project description:BackgroundThe relationship between ultrasongraphically derived estimates of fetal growth and educational attainment in the postnatal period is unknown. Results from previous studies focusing on cognitive ability, however, suggest there may be gestation-specific associations. Our objective was to model growth in fetal weight (EFW) and head circumference (HC) and identify whether growth variation in different periods was related to academic attainment in middle childhood.MethodsData come from the Born in Bradford (BiB) cohort study, which has performed data linkage to both routine antenatal scans and national academic attainment tests at age 6-7?years. Multilevel linear spline models were used to model EFW and HC. Random effects from these were related to Key Stage 1 (KS1) results in reading, writing, mathematics, science and a composite of all four (age 6-7?years), using ordinal logistic and logistic regression. Associations were adjusted for potential confounders, facilitated by directed acyclic graphs. Missing covariate data were imputed using multiple imputation.ResultsIn all, 6995 and 8438 children had complete KS1, and EFW and HC data, respectively. Positive associations were observed between both fetal weight in early pregnancy (14?weeks) and EFW growth in mid-pregnancy (14-26?weeks) and the individual KS1 outcomes. Furthermore, after adjustment for previous size and confounders, a 1-z score increase in growth in mid-pregnancy was associated with an 8% increased odds of achieving the expected standard for all KS1 outcomes [odds ratio (OR): 1.08, 95% confidence interval (CI): 1.02; 1.13]. Similar results were observed for HC, with generally larger effect sizes. Smaller associations were observed with growth in the early-third trimester, with no associations observed with growth in the later-third trimester.ConclusionsWe observed consistent positive associations between fetal size and growth in early and mid-gestation and academic attainment in childhood. The smaller and null associations with growth in the early-third and later-third trimester, respectively, suggests that early-mid gestation may be a sensitive period for future cognitive development.
| S-EPMC6208280 | biostudies-literature
Project description:BackgroundPrevious studies have shown markedly lower birth weight among infants of South Asian origin compared with those of White European origin. Whether such differences mask greater adiposity in South Asian infants and whether they persist across generations in contemporary UK populations is unclear. Our aim was to compare birth weight, skinfold thickness and cord leptin between Pakistani and White British infants and to investigate the explanatory factors, including parental and grandparental birthplace.MethodsWe examined the differences in birth weight and skinfold thickness between 4649 Pakistani and 4055 White British infants born at term in the same UK maternity unit and compared cord leptin in a subgroup of 775 Pakistani and 612 White British infants.ResultsPakistani infants were lighter (adjusted mean difference -234 g 95% CI -258 to -210) and were smaller in both subscapular and triceps skinfold measurements. The differences for subscapular and triceps skinfold thickness (mean z-score difference -0.27 95% CI -0.34 to -0.20 and -0.23 95% CI -0.30 to -0.16, respectively) were smaller than the difference in birth weight (mean z-score difference -0.52 95% CI -0.58 to -0.47) and attenuated to the null with adjustment for birth weight (0.03 95% CI -0.03 to 0.09 and -0.01 95% CI -0.08 to 0.05, respectively). Cord leptin concentration (indicator of fat mass) was similar in Pakistani and White British infants without adjustment for birth weight, but with adjustment became 30% higher (95% CI 17% to 44%) among Pakistani infants compared with White British infants. The magnitudes of difference did not differ by generation.ConclusionsDespite being markedly lighter, Pakistani infants had similar skinfold thicknesses and greater total fat mass, as indicated by cord leptin, for a given birth weight than White British infants. Any efforts to reduce ethnic inequalities in birth weight need to consider differences in adiposity and the possibility that increasing birth weight in South Asian infants might inadvertently worsen health by increasing relative adiposity.
| S-EPMC3859677 | biostudies-literature
Project description:BACKGROUND:Globally, international migration is increasing. Population growth, along with other demographic changes, may be expected to put new pressures on healthcare systems. Some studies across Europe suggest that emergency departments (EDs) are used more, and differently, by migrants compared to non-migrant populations, which may be a result of unfamiliarity with the healthcare systems and difficulties accessing primary healthcare. However, little evidence exists to understand how migrant parents, who are typically young and of childbearing age, utilise EDs for their children. This study aimed to examine the association between paediatric ED utilisation in the first 5 years of life and maternal migration status in the Born in Bradford (BiB) cohort study. METHODS AND FINDINGS:We analysed linked data from the BiB study-an ongoing, multi-ethnic prospective birth cohort study in Bradford. Bradford is a large, ethnically diverse city in the north of England. In 2017, more than a third of births in Bradford were to mothers who were born outside the UK. Between March 2007 and December 2010, pregnant women were recruited to BiB during routine antenatal care, and the children born to these mothers have been, and continue to be, followed over time to assess how social, genetic, environmental, and behavioural factors impact on health from childhood to adulthood. Data analysed in this study included baseline questionnaire data from BiB mothers, and Bradford Royal Infirmary ED episode data for their children. Main outcomes were likelihood of paediatric ED use (no visits versus at least 1 ED visit in the first 5 years of life) and ED utilisation rates (number and frequency of ED visits) for children who have accessed the ED. The main explanatory variable was mother's migrant status (foreign-born versus UK/Irish-born). Multivariable analyses (logistic and zero-truncated negative binomial regression) were conducted adjusting for socio-demographic and socio-economic factors. The final dataset included 10,168 children born between April 2007 and June 2011, of whom 35.6% were born to migrant mothers. Foreign-born mothers originated from South Asia (28.6%), Europe/Central Asia (3.2%), Africa (2.1%), East Asia/Pacific (1.1%), and the Middle East (0.6%). At recruitment the mothers ranged in age from 15 to 49 years old. Overall, 3,104 (30.5%) children had at least 1 ED visit in the first 5 years of life, with the highest proportion of visits being in the first year of life (36.7%). The proportion of children who visited the ED at least once was lower for children of migrant mothers as compared to children of non-migrant mothers (29.4% versus 31.2%). Children of migrant mothers were found to be less likely to visit the ED (odds ratio 0.88 [95% CI 0.80 to 0.97], p = 0.012). However, among children who visited the ED, the utilisation rate was significantly higher for children of migrant mothers (incidence rate ratio [IRR] 1.19 [95% CI 1.01 to 1.40], p = 0.040). Utilisation rates were higher for children born to mothers from Europe (IRR 1.71 [95% CI 1.07 to 2.71], p = 0.024) and established migrants (?5 years living in UK) (IRR 1.24 [95% CI 1.02 to 1.51], p = 0.032) compared to UK/Irish-born mothers. Important limitations include being unable to measure children's underlying health status and the urgency of ED attendance, as well as the analysis being limited by missing data. CONCLUSIONS:In this study we observed that there is no higher likelihood of first paediatric ED attendance in the first 5 years of life for children in the BiB cohort for migrant mothers. However, among ED users, children of migrant mothers attend the service more frequently than children of UK/Irish-born mothers. Our findings show that patterns of ED utilisation differ by mother's region of origin and time since arrival in the UK.
| S-EPMC7053707 | biostudies-literature