Abuse in Childhood and Cardiometabolic Health in Early Adulthood: Evidence From the Avon Longitudinal Study of Parents and Children

Background Although childhood abuse has been consistently associated with cardiovascular disease in later adulthood, its associations with cardiometabolic health in younger adults are poorly understood. We assessed associations between childhood physical, sexual, and psychological abuse and cardiometabolic outcomes at 18 and 25 years. Methods and Results We used data on 3223 participants of the ALSPAC (Avon Longitudinal Study of Parents and Children). Exposure to childhood abuse was self‐reported retrospectively at 22 years. We used linear regression to assess the associations between childhood abuse and cardiometabolic outcomes at 18 and 25 years. At 18 years, physical (β 1.35 kg/m 2 ; 95% CI, 0.66–2.05), sexual (β 0.57 kg/m 2 ; 95% CI 0.04–1.11), and psychological (β 0.47 kg/m 2 ; 95% CI 0.01–0.92) abuse were associated with higher body mass index. Physical abuse was also associated with lower high‐density lipoprotein cholesterol (β −0.07 mmol/L; 95% CI, −0.13 to −0.01) and higher C‐reactive protein (31%; 95% CI, 1%–69%), and sexual abuse was associated with higher heart rate (β 1.92 bpm; 95% CI 0.26–3.58). At age 25, all 3 types of abuse were additionally associated with higher insulin, and sexual abuse was associated with lower cholesterol (−0.14 mmol/L; 95% CI, −0.26 to −0.01). The age at which abuse occurred (<11or 11–17 years) had little influence on the associations, and when sex differences were evident, associations were stronger in men. Conclusions Childhood abuse is associated with negative cardiometabolic outcomes even by young adulthood. Further follow‐up will determine whether associations strengthen across the life course and whether sex differences persist, which is essential for targeting effective screening programs and early interventions in those who suffered abuse in childhood.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Home-based antibody testing results, October 2020. An emphasis on self-screening at a population level

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and offspring (Generation 1; G1) ever since. The study reacted rapidly to the COVID-19 pandemic, deploying online questionnaires in March and May 2020. Home-based antibody tests and a further questionnaire were sent to 5220 participants during a two-week period of October 2020. 4.2% (n=201) of participants reported a positive antibody test (3.2% G0s [n=81]; 5.6% G1s [n=120]). 43 reported an invalid test, 7 did not complete and 3 did not report their result. Participants uploaded a photo of their test to enable validation: all positive tests, those where the participant could not interpret the result and a 5% random sample were manually checked against photos. We report 92% agreement (kappa=0.853). Positive tests were compared to additional COVID-19 status information: 58 (1.2%) participants reported a previous positive test, 73 (1.5%) reported that COVID-19 was suspected by a doctor, but not tested and 980 (20.4%) believed they had COVID-19 due to their own suspicions. Of those reporting a positive result on our antibody test, 55 reported that they did not think they had had COVID-19. Results from antibody testing and questionnaire data will be complemented by health record linkage and results of other biological testing– uniting Pillar testing data with home testing and self-report. Data have been released as an update to the original datasets released in July 2020. It comprises: 1) a standard dataset containing all participant responses to all three questionnaires with key sociodemographic factors and 2) as individual participant-specific release files enabling bespoke research across all areas supported by the study. This data note describes the antibody testing, associated questionnaire and the data obtained from it.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture November 2020 – March 2021

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. The study has reacted rapidly and repeatedly to the coronavirus disease 2019 (COVID-19) pandemic, deploying online questionnaires throughout the pandemic. In November/December 2020, a fourth questionnaire was deployed asking about physical and mental health, lifestyle and behaviours, employment and finances. G0 participants were offered an online questionnaire between 17th November 2020 and 7th February 2021, while G1 participants were offered both online and paper questionnaires between 1st December 2020 and 19th March 2021. Of 15,844 invitations, 8,643 (55%) participants returned the questionnaire (3,101 original mothers [mean age 58.6 years], 1,172 original fathers/partners [mean age 61.5 years] and 4,370 offspring [mean age 28.4 years]). Of these 8,643 participants, 2,012 (23%) had not returned a previous COVID-19 questionnaire, while 3,575 (41%) had returned all three previous questionnaires. In this questionnaire, 300 participants (3.5%) reported a previous positive COVID-19 test, 110 (1.3%) had been told by a doctor they likely had COVID-19, and 759 (8.8%) suspected that they had had COVID-19. Based on self-reported symptoms, between October 2020 and February 2021 359 participants (4.2%) were predicted COVID-19 cases. COVID data is being complemented with linkage to health records and Public Health England pillar testing results as they become available. Data has been released as an update to the previous COVID-19 datasets. It comprises: 1) a standard dataset containing all participant responses to both questionnaires with key sociodemographic factors; and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study. This data note describes the fourth questionnaire and the data obtained from it.

Evidence of positive and negative selection associated with DNA methylation

Signatures of negative selection are pervasive amongst complex traits and diseases. However, it is unclear whether such signatures exist for DNA methylation (DNAm) that has been proposed to have a functional role in disease. We estimate polygenicity, SNP-based heritability and model the joint distribution of effect size and minor allele frequency (MAF) to estimate a selection coefficient (S) for 2000 heritable DNAm sites in 1774 individuals from the Avon Longitudinal Study of Parents and Children. Additionally, we estimate S for meta stable epi alleles and DNAm sites associated with aging and mortality, birthweight and body mass index. Quantification of MAF-dependent genetic architectures estimated from genotype and DNAm reveal evidence of positive (S>0) and negative selection (S<0) and confirm previous evidence of negative selection for birthweight. Evidence of both negative and positive selection highlights the role of DNAm as an intermediary in multiple biological pathways with competing function.

Stratification of adolescents across mental phenomena emphasizes the importance of transdiagnostic distress: a replication in two general population cohorts

Characterizing patterns of mental phenomena in epidemiological studies of adolescents can provide insight into the latent organization of psychiatric disorders. This avoids the biases of chronicity and selection inherent in clinical samples, guides models of shared aetiology within psychiatric disorders and informs the development and implementation of interventions. We applied Gaussian mixture modelling to measures of mental phenomena from two general population cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 3018) and the Neuroscience in Psychiatry Network (NSPN, n = 2023). We defined classes according to their patterns of both positive (e.g. wellbeing and self-esteem) and negative (e.g. depression, anxiety, and psychotic experiences) phenomena. Subsequently, we characterized classes by considering the distribution of diagnoses and sex split across classes. Four well-separated classes were identified within each cohort. Classes primarily differed by overall severity of transdiagnostic distress rather than particular patterns of phenomena akin to diagnoses. Further, as overall severity of distress increased, so did within-class variability, the proportion of individuals with operational psychiatric diagnoses. These results suggest that classes of mental phenomena in the general population of adolescents may not be the same as those found in clinical samples. Classes differentiated only by overall severity support the existence of a general, transdiagnostic mental distress factor and have important implications for intervention.

The ALSPAC fetal and neonatal resource: detailed data abstracted from the clinical records of the new-born

In a previous Data Note, we outlined the data obtained from clinical obstetric records concerning many details of the pregnancies resulting in the births of the children in the Avon Longitudinal Study of Parents and Children (ALSPAC). Here we describe the data that have been abstracted from medical records concerning the fetus and neonate. Full details concerning the selection biases regarding the data abstracted are outlined in the previous Data Note. The records that have been abstracted, and described in this Data Note, concern the health of the fetus (measured in relation to the results of fetal monitoring, presentation at various stages of pregnancy, and the method of delivery) as well as the status of the newborn immediately post-delivery. Details of signs, symptoms and treatments of this population of new-born babies, as recorded in the clinical records, are described for the time during which they were in hospital or under the care of a designated midwife. These data add depth to the information collected from elsewhere concerning this period of the child’s life: from the questionnaires completed at the time by the mother; and clinical details from neonatal intensive or special care units which will be detailed in a further Data Note.

A multi-variant recall-by-genotype study of the metabolomic signature of body mass index

Objective: We estimated the effect of body mass index (BMI) on circulating metabolites in young adults using a recall-by-genotype (RbG) study design. Methods: An RbG study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low/high genetic liability for higher BMI defined by a genetic score (GS). Regression analyses were performed to investigate the association between BMI GS groups and relative abundance of 973 metabolites. Results: After correction for multiple testing, 29 metabolites were associated with BMI GS group. Bilirubin was amongst the most strongly associated metabolites with reduced levels measured in individuals with the highest BMI GS (beta=-0.32, 95% confidence interval (CI): -0.46, -0.18, Benjamini-Hochberg (BH) adjusted p=0.005). We observed associations between BMI GS group and levels of several potentially diet-related metabolites including hippurate which had lower mean abundance in individuals in the high BMI GS group (beta=-0.29, 95% CI: -0.44, -0.15, BH adjusted p=0.008). Conclusions: Together with existing literature our results suggest a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Antibody testing results, April – June 2021

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. The study reacted rapidly and repeatedly to the coronavirus disease 2019 (COVID-19) pandemic, deploying multiple online questionnaires and a previous home-based antibody test in October 2020. A second antibody test, in collaboration with ten other longitudinal population studies, was completed by 4,622 ALSPAC participants between April and June 2021. Of participants with a valid spike protein antibody test result (4,241; 8.2% void), indicating antibody response to either COVID-19 vaccination or natural infection, 3,172 were positive (74.8%). Generational differences were substantial, with 2,463/2,555 G0 participants classified positive (96.4%) compared to 709/1,686 G1 participants (42.1%). Of participants with a valid nucleocapsid antibody test result (4,199; 9.2% void), suggesting potential and recent natural infection, 493 were positive (11.7%); with 248/2,526 G0 participants (9.8%) and 245/1,673 G1 participants (14.6%) testing positive, respectively. We also compare results for this round of testing to that undertaken in October 2020. Future work will combine these test results with additional sources of data to identify participants’ COVID-19 infection and vaccination status. These ALSPAC COVID-19 serology data are being complemented with linkage to health records and Public Health England pillar testing results as they become available, in addition to four previous questionnaire waves and a prior antibody test. Data have been released as an update to the previous COVID-19 datasets. These comprise: 1) a standard dataset containing all participant responses to all four previous questionnaires with key sociodemographic factors; and 2) individual participant-specific release files enabling bespoke research across all areas supported by the study. This data note describes the second ALSPAC antibody test and the data obtained from it.

Are dietary patterns in early childhood associated with alcohol consumption at the age of 17? Analysis of data from the Avon Longitudinal Study of Children and Parents (ALSPAC) prospective cohort study

Objective To examine the relationship between a posteriori dietary patterns in early childhood and alcohol consumption in adolescence. Design Data was obtained from the Avon Longitudinal Study of Children and Parents (ALSPAC) prospective cohort study. Dietary information was obtained using food frequency questionnaires at ages 3 and 7 years. The association between dietary patterns, derived using Principal Components Analysis (PCA) and the Alcohol Use Disorders Identification Test (AUDIT) scores (to assess harmful intake) and frequency of alcohol consumption at 17 years were examined. Secondary analysis considered sugar intake as a percentage of total energy intake. Setting Women who gave birth between 1 April 1991 and 31 December 1992 in the Avon area in southwest England were eligible for the ALSPAC cohort study. Participants 14,541 pregnancies were enrolled in ALSPAC during its initial recruitment phase. For this analysis, complete data was available for between 3148 and 3520 participants. Results Adherence to the “healthy” dietary pattern at both 3 and 7 years of age was positively associated with consuming more than one alcoholic drink per week at 17 years, whilst adherence to the ‘traditional’ dietary pattern at both ages was protective of harmful alcohol intake at 17. Sugar intake was not associated with either alcohol outcome after adjustment for ethnicity, maternal level of education, parental social class and maternal AUDIT score. Conclusions For the population studied, changes to diet in early childhood are unlikely to have an impact on harmful alcohol use in adolescence given the lack of consistency across the results.