Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort.
ABSTRACT: Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal ( Saccharomyces cerevisiae); protozoan ( Toxoplasma gondii and surface antigen 1 of T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler's virus); bacteria ( Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes.
Project description:Depression during adolescence is associated with a number of negative outcomes in later life. Research has examined the longitudinal nature of adolescent depression in order to identify patterns of depressive mood, the early antecedents and later consequences. However, rich longitudinal data is needed to better address these questions. The Avon Longitudinal Study of Parents and Children (ALSPAC) is an intergenerational birth cohort with nine repeated assessments of depressive symptoms throughout late childhood, adolescence and young adulthood. Depressive symptoms are measured using the Short Mood and Feelings Questionnaire (SMFQ). Many studies have used ALSPAC to examine the longitudinal nature of depressive symptoms in combination with the wealth of early life exposure and later outcome data. This data note provides a summary of the SMFQ data, where the data are stored in ALSPAC, the characteristics and distribution of the SMFQ, and highlights some considerations for researchers wanting to use the SMFQ data in ALSPAC.
Project description:Background: The Avon Longitudinal Study of Parents and Children-Generation 2 (ALSPAC-G2) was set up to provide a unique multi-generational cohort. It builds on the existing ALSPAC resource, which recruited 14,541 pregnancies to women resident in the South West of England who were expected to deliver between 01/04/1991 and 31/12/1992. Those women and their partners (Generation 0; ALSPAC-G0) and their offspring (ALSPAC-G1) have been followed for the last 26 years. This profile describes recruitment and data collection on the next generation (ALSPAC-G2)-the grandchildren of ALSPAC-G0 and children of ALSPAC-G1. Recruitment: Recruitment began on the 6 th of June 2012 and we present details of recruitment and participants up to 30 th June 2018 (~6 years). We knew at the start of recruitment that some ALSPAC-G1 participants had already become parents and ALSPAC-G2 is an open cohort; we recruit at any age. We hope to continue recruiting until all ALSPAC-G1 participants have completed their families. Up to 30 th June 2018 we recruited 810 ALSPAC-G2 participants from 548 families. Of these 810, 389 (48%) were recruited during their mother's pregnancy, 287 (35%) before age 3 years, 104 (13%) between 3-6 years and 30 (4%) after 6 years. Over 70% of those invited to early pregnancy, late pregnancy, second week of life, 6-, 12- and 24-month assessments (whether for their recruitment, or a follow-up, visit) have attended, with attendance being over 60% for subsequent visits up to 7 years (to few are eligible for the 9- and 11-year assessments to analyse). Data collection: We collect a wide-range of social, lifestyle, clinical, anthropometric and biological data on all family members repeatedly. Biological samples include blood (including cord-blood), urine, meconium and faeces, and placental tissue. In subgroups detailed data collection, such as continuous glucose monitoring and videos of parent-child interactions, are being collected.
Project description:Oral health data in large longitudinal cohort studies is rarely collected at multiple time-points. This type of data is important for assessing oral health trajectories and their determinants. This data resource includes self-report questionnaire data on up to 4,222 young adults at approximately 23 years of age from the Avon Longitudinal Study of Parents and Children (ALSPAC). The resource includes questions on dental attendance, tooth restorations and extractions, third molars (wisdom teeth) and mouth ulcers. It follows on from similar questionnaires at ages 7, 10 and 17 years. The ALSPAC study includes extensive phenotype, genetic, epigenetic and metabolomic data from the participants included in this questionnaire plus their mothers and fathers.
Project description:Background: Exposure to adverse childhood experiences (ACEs) is a risk factor for poor later life health. Here, we describe the ACE variables measured in the children of the Avon Longitudinal Study of Parents and Children (ALSPAC) study, and a method used to derive summary measures and deal with missing data in them. Methods: The ALSPAC data catalogue (59 608 variables) was searched in September 2017 for measures on adversity exposure between birth and 18 years. 6140 adversity questions were then screened for conforming to our ACE definitions and suitability for dichotomisation. This screening identified 541 questions on ten 'classic' ACEs (sexual, physical or emotional abuse, emotional neglect, substance abuse by the parents, parental mental illness or suicide attempt, violence between parents, parental separation, bullying and parental criminal conviction) and nine additional ACEs (bond between parent and child, satisfaction with neighbourhood, social support for the parent, social support for the child, physical illness of a parent, physical illness of the child, financial difficulties, low social class and violence between child and partner). These were used to derive a binary construct for exposure to each ACE. Finally, as cumulative measures of childhood adversity, different combinations of the 19 ACE constructs were summed to give total adversity scores. An appropriate strategy for multiple imputation was developed to deal with the complex patterns of missing data. Results: The ACE constructs and ACE-scores for exposure between birth and 16 years had prevalence estimates that were comparable to previous reports (for instance 4% sexual abuse, 18% physical abuse, 25% bullied, 32% parental separation). Conclusions: ACE constructs, derived using a pragmatic approach to handle the high dimensional ALSPAC data, can be used in future analyses on childhood adversity in ALSPAC children.
Project description:Common infectious agents, such as Toxoplasma gondii (T. gondii) and several human herpes viruses, have been linked to increased risk of self-harm. The aim of this study was to investigate the associations between self-harm and seropositivity to T. gondii, Epstein-Barr virus (EBV), Herpes Simplex virus Type 1 (HSV-1), and Cytomegalovirus (CMV). IgM and IgG antibodies to these infections were measured in the Health 2000 project nationally representative of the whole Finnish adult population, and 6250 participants, age 30 and over, were followed for 15 years via registers. In addition, lifetime suicidal ideation and suicide attempts based on medical records and interview were assessed within a subsample of 694 participants screened to a substudy for possible psychotic symptoms or as controls. Among the 6250 participants, 14 individuals died of suicide and an additional 4 individuals had a diagnosis of intentional self-harm during follow-up. Serological evidence of lifetime or acute infections was not found to be associated with these suicidal outcomes. However, in the subsample, those seropositive for CMV had fewer suicide attempts compared to those seronegative, adjusting for gender, age, educational level, childhood family size, regional residence, CRP, and screen status (OR for multiple attempts?=?0.40, 95% confidence interval 0.20?0.83, p?=?0.014). To conclude, common infections were not associated with risk of death by suicide or with self-harm diagnoses at a 15-year follow-up in the general population sample. Our finding of an increased number of suicide attempts among persons seronegative for CMV calls for further research.
Project description:Background: Early life experiences can have a significant impact on an individual's later behaviour, the way they view the world, their beliefs and their success at forming strong interpersonal relationships. These factors may subsequently influence the way that the individual may parent their children, which in turn may have an effect on their child's behaviour, mental health and world view. Research has linked early traumatic life experiences in the parent's childhood to disorganised attachment to their own child. In this paper we describe the data collected from parents enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) on traumatic events experienced during their childhood, so that it can act as a resource for researchers in the future when considering outcomes on the adult, their children and grandchildren. Methods: Data were collected via multiple questionnaires completed by parents enrolled into the ALSPAC study. During pregnancy and post-delivery, questionnaires were administered between 1990 and 1992 via post to the study mothers and their partners. Data were collected on life events including bereavement, sexual abuse, physical abuse, abandonment, neglect, memories of childhood and accidents. Other reports of traumatic events in childhood were reported by parents using free text. This can be made available to researchers for coding on request.
Project description:The FRAXA and FRAXE alleles of the FMR1 and FMR2 genes located on the X chromosome contain varying numbers of trinucleotide repeats. Large numbers of repeats at FRAXA (full mutations) manifest as Fragile X syndrome, associated with mental impairment that affects males more severely. In this paper, we present the dataset of frequencies of FRAXA and FRAXE repeat size extracted from DNA samples collected from boys enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). DNA data were extracted from samples collected in ALSPAC clinics from several types of samples: cord blood, venepuncture blood taken at 43 months, 61 months, seven years or nine years. The DNA was amplified at FRAXA and FRAXE using fluorescent PCR in the Wessex Regional Genetics Laboratory, Salisbury District Hospital. The mean repeat size for FRAXA is 28.92 (S.D. 5.44), the median 30 and the range 8 to 68. There were particularly high numbers of boys with repeat sizes of 20 (10.67%) and 23 (7.35%). The mean repeat size for FRAXE is 17.41 (S.D. 3.94), with median of 16 and range of 0 to 61. There is a relatively high degree of variation of the FRAXA repeat size particularly and we suggest the extensive data available from the ALSPAC study opens up areas of research into understanding phenotypes associated with relatively unexplored repeat sizes. This could be particularly interesting for the lower repeat sizes occurring with high frequency at FRAXA in this population. As the data can be linked to exposures and phenotypes, it will provide a resource for researchers worldwide.
Project description:BACKGROUND AND AIMS:Familial hypercholesterolaemia (FH) is an autosomal-dominant disease with frequency of 1/500 to 1/250 that leads to premature coronary heart disease. New approaches to identify FH mutation-carriers early are needed to prevent premature cardiac deaths. In a cross-sectional study of the Avon Longitudinal Study of Parents and Children (ALSPAC), we evaluated the biochemical thresholds for FH screening in childhood, and modelled a two-stage biochemical and sequencing screening strategy for FH detection. METHODS:From 5083 ALSPAC children with cholesterol measurement at age nine years, FH genetic diagnosis was performed in 1512 individuals, using whole-genome or targeted sequencing of known FH-causing genes. Detection rate (DR) and false-positive rate (FPR) for proposed screening thresholds (total-cholesterol > 1.53, or LDL-C > 1.84 multiples of the median (MoM)) were assessed. RESULTS:Six of 1512 sequenced individuals had an FH-causing mutation of whom five had LDL-C > 1.84 MoM, giving a verification-bias corrected DR of 62.5% (95% CI: 25-92), with a FPR of 0.2% (95% CI: 0.1-0.4). The DR for the TC cut-point of 1.53 MoM was 25% (95% CI: 3.2-65.1) with a FPR of 0.4% (95% CI: 0.2-0.6). We estimated 13 of an expected 20 FH mutation carriers (and 13 of the 20 parental carriers) could be detected for every 10,000 children screened, with false-positives reliably excluded by addition of a next generation sequencing step in biochemical screen-positive samples. CONCLUSIONS:Proposed cholesterol thresholds for childhood FH screening were less accurate than previously estimated. A sequential strategy of biochemical screening followed by targeted sequencing of FH genes in screen-positive children may help mitigate the higher than previously estimated FPR and reduce wasted screening of unaffected parents.
Project description:The purpose of this study is to identify and analyse the putative promoter motifs in the bovine herpes virus which causes several diseases in cattle worldwide including bovine mastitis with large economic impact on dairy industry. Bovine mastitis caused due to virus is often neglected as bacterial infections are held mainly responsible for the disease. Therefore, in this in silico investigation with all the existing experimental data a total of 147 promoter were identified along with their sequences from three genome viz bovine herpes virus 1 (BHV), bovine herpes virus 4 and bovine herpes virus 5, out of which 39 promoters were from bovine herpes virus 4 (BHV 4), 95 from BHV1 and 13 from BHV5 and it was observed that BHV1 and BHV5 have a close evolutionary history. However, they belong to the same subfamily and size of the genome and GC% of BHV1 and BHV5 was almost equal and very high compare to that of BHV4. This analysis may help in designing the live attenuated vaccine against BHV causing bovine mastitis that reduces the incidence of bovine mastitis. Identification of promoters may also help in designing of expression vectors which help in better understanding of the regulation of gene expression. In the era of large genomics and proteomics prediction of promoters in the whole genome is crucial for the advancement of drug discovery and gene therapy.
Project description:The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. However, studies reporting associations between mtDNA haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification and performing inadequate statistical tests. In this study we investigated the association of mtDNA haplogroups of European origin with several breast cancer risk factors in mothers and children of the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort that enrolled over 14,000 pregnant women in the Southwest region of the UK. Risk factor data were obtained from questionnaires, clinic visits and blood measurements. Information on over 40 independent breast cancer risk factor-related variables was available for up to 7781 mothers and children with mtDNA haplogroup data in ALSPAC. Linear and logistic regression models adjusted for age, sex and population stratification principal components were evaluated. After correction for multiple testing we found no evidence of association of European mtDNA haplogroups with any of the breast cancer risk factors analysed. Mitochondrial DNA haplogroups are unlikely to underlie susceptibility to breast cancer that occurs via the risk factors examined in this study of a population of European ancestry.