Avon Longitudinal Study Of Parents Research Articles

Exploring the importance of family socio-economic position on the association between parental BMI and offspring BMI trajectories

PurposeWe aimed to investigate the associations between parental BMI and offspring BMI trajectories and to explore whether the parent-offspring BMI growth trajectory association differed according to family SEP or social mobility. MethodsWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Children’s weight and height were collected from 1 to 18 years. Parents’ height and weight were reported pre-pregnancy. We assessed family SEP by measuring parents’ and grandparents’ educational attainment, social class, and social mobility by changes in education attainment across generations. Multilevel models were used to develop trajectories and assess patterns of change in offspring BMI, to associate parental BMI with these trajectories, and explore whether these associations differed by family SEP and social mobility. Results13,612 children were included in the analyses. The average BMI of offspring whose parents were overweight or obese was higher throughout childhood and adolescence, compared to those with parents of normal BMI. Parental and grandparental low SEP were associated with higher child BMI, but there was little evidence of modification of parent-offspring associations. For example, at age 15 years the predicted mean BMI difference between children of overweight or obese mothers versus normal-weight mothers was 12.5 % (95 %CI: 10.1 % to 14.7 %) and 12.2 % (95 %CI: 10.3 % to 13.7 %) for high and low grandparental SEP, respectively. DiscussionThese findings strengthen the evidence that higher parental BMI and lower family SEP were associated with higher offspring BMI, but we did not observe strong evidence that family SEP modifies the parental-offspring BMI association.

Analyses Using Multiple Imputation Need to Consider Missing Data in Auxiliary Variables.

Auxiliary variables are used in multiple imputation (MI) to reduce bias and increase efficiency. These variables may often themselves be incomplete. We explored how missing data in auxiliary variables influenced estimates obtained from MI. We implemented a simulation study with three different missing data mechanisms for the outcome. We then examined the impact of increasing proportions of missing data and different missingness mechanisms for the auxiliary variable on bias of an unadjusted linear regression coefficient and the fraction of missing information. We illustrate our findings with an applied example in the Avon Longitudinal Study of Parents and Children. We found that where complete records analyses were biased, increasing proportions of missing data in auxiliary variables, under any missing data mechanism, reduced the ability of MI including the auxiliary variable to mitigate this bias. Where there was no bias in the complete records analysis, inclusion of a missing not at random auxiliary variable in MI introduced bias of potentially important magnitude (up to 17% of the effect size in our simulation). Careful consideration of the quantity and nature of missing data in auxiliary variables needs to be made when selecting them for use in MI models.

Longitudinal relationships between early-life homelessness and school-aged asthma and wheezing

BackgroundHomelessness is a disruptive life event with profound impacts on children’s health. It remains unclear, however, whether homelessness in early life has an enduring association with asthma and wheezing among...

Longitudinal characterization of impulsivity phenotypes boosts signal for genomic correlates and heritability.

Genomic correlates of impulsivity have been identified in several genome-wide association studies (GWAS) using cross-sectional designs, but no studies have investigated the molecular genetic correlates of impulsivity phenotypes using longitudinally constructed traits. In 3860 unrelated European participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), we constructed longitudinal phenotypes for delay discounting and impulsive personality traits (as measured by the UPPS-P impulsive behavior scales) via assessment at ages 24, 26, and 28. We conducted GWASs of impulsivity using both cross-sectional and longitudinal phenotypes, estimated heritability and their phenotypic and genetic correlations, and evaluated their association with recently-developed polygenic risk scores (PRSs) for the impulsivity indicators themselves and also related psychiatric conditions. Latent growth curve modeling revealed a stable intercept over time for all impulsivity phenotypes. High genetic correlation of cross-sectional measures over time suggested a stable genetic component for delay discounting (rg = 0.53-0.99) and sensation seeking (rg = 0.99). Heritability estimates of the stable longitudinal phenotypes substantively improved as compared to their cross-sectional counterparts, revealing a significant SNP-heritability for delay discounting (0.22; p = 0.03) and sensation seeking (0.35; p = 0.0007). Consistent with previous reports, GWAS and gene-based analyses revealed associations between specific longitudinal impulsivity indicators and CADM2 and NCAM1 genes. The PRSs for the impulsivity indicators and disorders related to self-regulation were also significantly associated with longitudinal impulsivity traits. Finally, we validated the associations between longitudinal impulsivity phenotypes and their PRSs in an independent 13-wave longitudinal study (n = 1019) and the benefit of longitudinal phenotypes in simulation studies. In this first longitudinal genetic study of impulsivity traits, the results revealed stable genomic correlates of delay discounting and sensation seeking over time and further validated the utility of recently-developed PRSs, both in relation to the observed traits and in connecting them to psychiatric disorders. More generally, these findings support using latent intercepts as novel longitudinal phenotypes to boost signal for heritability and genomic correlates of mechanisms contributing to psychiatric disease liability.

The Chain Mediation Effect of Victimization and Neuroticism on the Association Between Sexual Orientation and Depressive Symptoms: A Prospective Birth Cohort Study.

This study tested whether sexual orientation differences in depressive symptoms were partially explained by the chain mediation effect of neuroticism and victimization. Using the Avon Longitudinal Study of Parents and Children from the UK (N = 4647, 36.52% men, 88% White), self-reported neuroticism, sexual orientation, and depressive symptoms were measured at age 13.5, 21, and 22years, respectively. Childhood abuse between birth and age 11years and the individuals' experiences of being bullied at age 17.5years were measured as the components of victimization. Structural equation modeling was used to analyze the data. Non-heterosexual individuals reported higher depressive symptoms than heterosexual individuals, with a total effect (standardized path coefficient) of 0.590 and 0.768 for men and women, respectively. This association was partially explained by childhood abuse (indirect effect = 0.043 and 0.046 for men and women, respectively) and neuroticism directly (indirect effect = 0.036 and 0.056 for men and women, respectively). Sexual orientation differences in depressive symptoms were also partially explained by a path through increased risk of experiencing childhood abuse leading to higher levels of neuroticism (indirect effect = 0.004 and 0.009 for men and women, respectively) and by a path through higher levels of neuroticism leading to increased risk of being bullied (indirect effect = 0.004 and 0.002 for men and women, respectively). The findings suggest that while some of the association between sexual orientation and depression might be explained by neuroticism and experiences of victimization measured prospectively, these factors do not account for most of this relationship.

Later eating rhythm measured in children at 7 years of age in the ALSPAC cohort.

Later eating rhythm (LER) refers to later timing, greater energy intake (EI), and higher frequency of eating occasions (meal/snack) in the evening. The significance of LER in child health is becoming increasingly recognised. However, the lack of consensus regarding definitions of LER make it challenging to fully comprehend its role. This data note describes LER variables derived in the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing birth cohort which enrolled 14,541 pregnant women living in Avon, UK, with an expected date of delivery between April 1991 - December 1992. When children were 7 years, parents completed a structured 3-day food diary, recording all foods/drinks consumed over 3 days (preferably 1 weekend day and 2 weekdays). Data was available for 7,285 children (50.1% response rate). A subsample of 4,869 children had exact time of eating occasions added to the existing database, which only included broad indications of eating timing based on 2-7 hour long meal slots. 13 LER variables were derived for the entire week and weekdays/weekend days separately. These comprise: 1) eating around individual bedtime (number days); 2) eating around average bedtime (number days); 3) time of evening main meal (hrs:mins); 4) time of last eating occasion (hrs:mins); 5) EI in the evening (percentage of total daily energy intake, %TDEI); 6) EI within 2hrs before bedtime (%TDEI); 7) EI for evening main meal (%TDEI); 8) EI for evening snacks (%TDEI); 9) Night eating1 (NE1): eating over 30% of total daily energy intake after 18:00 (number days); 10) NE2: eating over 25% of total daily energy intake within 2hrs before bedtime (number days); 11) eating frequency after 17:00 (number of eating occasions); 12) regularity of dinner (number of days); 13) frequency of evening snacks (number days). We describe the derivation, prevalence and inter-corelations between LER variables.

Trajectories of Inflammation in Youth and Risk of Mental and Cardiometabolic Disorders in Adulthood

Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes. To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood. In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024. Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation. Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score. A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years. Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.

Mapping associations of polygenic scores with autistic and ADHD traits in a single city region.

The genetic and environmental aetiology of autistic and Attention Deficit Hyperactivity Disorder (ADHD) traits is known to vary spatially, but does this translate into variation in the association of specific common genetic variants? We mapped associations between polygenic scores for autism and ADHD and their respective traits in the Avon Longitudinal Study of Parents and Children (N = 4,255-6,165) across the area surrounding Bristol, UK, and compared them to maps of environments associated with the prevalence of autism and ADHD. Our results suggest genetic associations vary spatially, with consistent patterns for autistic traits across polygenic scores constructed at different p-value thresholds. Patterns for ADHD traits were more variable across thresholds. We found that the spatial distributions often correlated with known environmental influences. These findings shed light on the factors that contribute to the complex interplay between the environment and genetic influences in autistic and ADHD traits.

Adolescent Psychotic Experiences and Adverse Mental Health Outcomes in Adulthood in a General Population Sample.

This study estimated risk of incident mental disorders in adulthood associated with both transient and persistent adolescent psychotic experiences (PEs). A nested case-control design was used within the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study which recruited expectant mothers from 1991-1992. Participants consisted of 8822 offspring of ALSPAC mothers who completed the Psychosis-like Symptoms Interview Questionnaire (PLIKSi-Q). PEs were assessed using the PLIKSi-Q. Depressive disorders were assessed using the Short Mood and Feelings Questionnaire (SMFQ), anxiety disorders using the General Anxiety Disorder Assessment and the Clinical Interview Schedule-Revised, and psychotic disorder using the PLIKSi. Risk of incident depressive disorder, GAD, psychotic disorder, and past-year suicide attempts were compared amongst participants who had ever versus never reported a PE and those who reported persistent versus transient PEs. Adolescent PEs were associated with increased risk for incident depressive disorder (adjusted hazard ratio (aHR) = 1.62, 95% CI = 1.42, 1.84), GAD (aHR 1.23, 95% CI = 1.03, 1.47), psychotic disorder (adjusted odds ratio (aOR) = 5.08, 95% CI = 2.02, 12.79), and past-year suicide attempts (aHR = 2.56, 95% CI = 1.97, 3.25). Persistent PEs were associated with increased risk for depressive disorder (aHR = 1.81, 95% CI = 1.55, 2.12), generalized anxiety disorder (aHR = 1.34, 95% CI = 1.07, 1.68), and psychotic disorder (aOR = 7.39, 95% CI = 2.43, 22.19) but not past-year suicide attempts. Adolescent PEs are a risk factor for multiple mental disorders and suicide attempts, with persistent PEs conferring greater risk. Identifying interventions for adolescents who report PEs, particularly persistent PEs, could lessen the burden of multiple mental health disorders and suicide attempts.

The role of body image dissatisfaction in the relationship between body size and disordered eating and self-harm: complimentary Mendelian randomization and mediation analyses.

Disordered eating and self-harm commonly co-occur in young people suggesting potential for shared underlying causes. Body image dissatisfaction (BID) has been recognised as a psychological correlate of body size, associated with both disordered eating and self-harm. However, the investigation into etiological pathways early in the lifecourse to provide detail on how body size and BID may foster disordered eating and self-harm remains largely unexplored. Employing data from two large population-based cohorts, the UK Biobank and the Avon Longitudinal Study of Parents And Children (ALSPAC), we conducted bidirectional Mendelian randomization (MR) to determine the causal direction of effect between genetically predicted prepubertal body size and two measures of BID indicating (i) desire to be smaller, and (ii) desire to be larger. We then used multivariable regression followed by counterfactual mediation analyses. Bidirectional MR indicated robust evidence that increased genetically predicted prepubertal body size increased desire to be smaller and decreased desire to be larger. Evidence for the reverse causal direction was negligible. These findings remained very similar across sensitivity analyses. In females and males, multivariable regression analyses demonstrated that being overweight increased the risk of disordered eating (risk ratio (RR), 95% confidence interval (CI): 1.19, 1.01 to 1.40 and 1.98, 1.28 to 3.05, respectively) and self-harm (RR, 95% CI: 1.35, 1.04 to 1.77 and 1.55, 0.86 to 2.81, respectively), while being underweight was protective against disordered eating (RR, 95% CI: 0.57, 0.40 to 0.81 and 0.81, 0.38 to 1.73, respectively). There was weak evidence of an increase in the risk of self-harm among underweight individuals. Mediation analyses indicated that the relationship between being overweight and subsequent disordered eating was largely mediated by the desire to be smaller. Our research carries important public health implications, suggesting distinct risk profiles for self-harm and disordered eating in relation to weight and body image. In addition, a better understanding of genetically predicted prepubertal BID may be valuable in the prevention and treatment of disordered eating and self-harm in adolescence.

Investigating the neurodevelopmental correlates of early adolescent-onset emotional problems

BackgroundEmotional problems (EPs) increase sharply after mid-adolescence. Earlier EPs are associated with poorer long-term outcomes, and their underlying mechanisms may differ to later-onset EPs. Given an established relationship between ADHD, autism, and later depression, we aimed to examine associations between neurodevelopmental conditions and correlates and early adolescent-onset EPs. MethodsAdolescents in two UK population cohorts, Avon Longitudinal Study of Parents and Children (ALSPAC) and Millennium Cohort Study (MCS), were included. Individuals scoring >6 on the Strengths and Difficulties Questionnaire (SDQ) emotional problems subscale between ages 11–14 were defined as having early adolescent-onset EP, whilst those scoring >6 for the first time at 16–25 were defined as having later-onset EP. We tested associations between early adolescent-onset EP (total cases = 887, controls = 19,582) and ICD-10/DSM-5 neurodevelopmental conditions and known correlates, including: sex, birth complications, low cognitive ability, special educational needs (SEND), and epilepsy. Analyses were conducted separately in ALSPAC and MCS then meta-analysed. ResultsIn the meta-analysis of both cohorts, early adolescent-onset EPs were associated with female sex and greater likelihood of low cognitive ability, SEND, autism, ADHD, and reading difficulties. Compared to later-onset EP, early adolescent-onset EPs were associated with male sex, low cognitive ability, SEND, epilepsy, ASD, ADHD, and reading difficulties. LimitationsA clinical definition of depression/anxiety was available only in ALSPAC, instead we primarily defined EP via questionnaires, which capture a broader phenotype. ConclusionsIndividuals with early adolescent-onset EP are likely to have a co-occurring neurodevelopmental condition. Clinicians should consider assessing for neurodevelopmental conditions in young adolescents with EPs.

Associations between prenatal stress with offspring inflammation, depression and anxiety

PurposeFew longitudinal studies have investigated the mediating role of inflammation during childhood in associations between prenatal maternal stress and adolescent mental health. The objective of this study was to examine the associations between prenatal maternal stress, concentrations of immune markers at age 9, and symptoms of generalized anxiety disorder (GAD) and depression during adolescence. MethodsThis study included 3723 mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Prenatal maternal stress was examined using 55 items measured during pregnancy. Inflammation was assessed using serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP) when children were 9 years old. GAD and depression were assessed when children were 16 and 18 years of age, respectively. Analyses comprised of structural equation models. ResultsPrenatal maternal stress was associated with higher concentrations of IL-6 in childhood, and with greater symptoms of depression and GAD in adolescence. However, we did not observe associations between prenatal maternal stress and CRP; also, CRP and IL-6 were not associated with depression and GAD. There was no evidence that CRP and IL-6 mediated the associations between prenatal maternal stress and either GAD or depression. ConclusionsPrenatal maternal stress is associated with IL-6 levels in childhood, and with GAD and depression during adolescence. Future studies should examine immune activity at multiple points during development in relation to mental health into adulthood to determine whether inflammation at different points during development could increase risk for mental health problems among children whose mothers experienced significant stressors during pregnancy.

Exploring pleiotropy in Mendelian randomisation analyses: What are genetic variants associated with 'cigarette smoking initiation' really capturing?

Genetic variants used as instruments for exposures in Mendelian randomisation (MR) analyses may have horizontal pleiotropic effects (i.e., influence outcomes via pathways other than through the exposure), which can undermine the validity of results. We examined the extent of this using smoking behaviours as an example. We first ran a phenome-wide association study in UK Biobank, using a smoking initiation genetic instrument. From the most strongly associated phenotypes, we selected those we considered could either plausibly or not plausibly be caused by smoking. We examined associations between genetic instruments for smoking initiation, smoking heaviness and lifetime smoking and these phenotypes in UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC). We conducted negative control analyses among never smokers, including children. We found evidence that smoking-related genetic instruments were associated with phenotypes not plausibly caused by smoking in UK Biobank and (to a lesser extent) ALSPAC. We observed associations with phenotypes among never smokers. Our results demonstrate that smoking-related genetic risk scores are associated with unexpected phenotypes that are less plausibly downstream of smoking. This may reflect horizontal pleiotropy in these genetic risk scores, and we would encourage researchers to exercise caution this when using these and genetic risk scores for other complex behavioural exposures. We outline approaches that could be taken to consider this and overcome issues caused by potential horizontal pleiotropy, for example, in genetically informed causal inference analyses (e.g., MR) it is important to consider negative control outcomesand triangulation approaches, to avoid arriving at incorrect conclusions.

Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns

Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations. To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth. For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023. A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure. Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes. This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (β, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (β, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA. The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

Later eating rhythm measured in children at 7 years of age in the ALSPAC cohort

Later eating rhythm (LER) refers to later timing, greater energy intake (EI), and higher frequency of eating occasions (meal/snack) in the evening. The significance of LER in child health is becoming increasingly recognised. However, the lack of consensus regarding definitions of LER make it challenging to fully comprehend its role. This data note describes LER variables derived in the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing birth cohort which enrolled 14,541 pregnant women living in Avon, UK, with an expected date of delivery between April 1991 - December 1992. When children were 7 years, parents completed a structured 3-day food diary, recording all foods/drinks consumed over 3 days (preferably 1 weekend day and 2 weekdays). Data was available for 7,285 children (50.1% response rate). A subsample of 4,869 children had exact time of eating occasions added to the existing database, which only included broad indications of eating timing based on 2-7 hour long meal slots. 13 LER variables were derived for the entire week and weekdays/weekend days separately. These comprise: 1) eating around individual bedtime (number days); 2) eating around average bedtime (0number days); 3) time of evening main meal (hrs:mins); 4) time of last eating occasion (hrs:mins); 5) EI in the evening (percentage of total daily energy intake, %TDEI); 6) EI within 2hrs before bedtime (%TDEI); 7) EI for evening main meal (%TDEI); 8) EI for evening snacks (%TDEI); 9) Night eating1 (NE1): eating over 30% of total daily energy intake after 18:00 (number days); 10) NE2: eating over 25% of total daily energy intake within 2hrs before bedtime (number days); 11) eating frequency after 17:00 (number of eating occasions); 12) regularity of dinner (0, 1, 2, 3 days); 13) frequency of evening snacks (number days). We describe the derivation, prevalence and inter-corelations between LER variables.

Childhood Adversity and Incident Psychotic Experiences in Early Adulthood: Cognitive and Psychopathological Mediators.

Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood. We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula. In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results. Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences.

Using instruments for selection to adjust for selection bias in Mendelian randomization.

Selection bias is a common concern in epidemiologic studies. In the literature, selection bias is often viewed as a missing data problem. Popular approaches to adjust for bias due to missing data, such as inverse probability weighting, rely on the assumption that data are missing at random and can yield biased results if this assumption is violated. In observational studies with outcome data missing not at random, Heckman's sample selection model can be used to adjust for bias due to missing data. In this paper, we review Heckman's method and a similar approach proposed by Tchetgen Tchetgen and Wirth (2017). We then discuss how to apply these methods to Mendelian randomization analyses using individual-level data, with missing data for either the exposure or outcome or both. We explore whether genetic variants associated with participation can be used as instruments for selection. We then describe how to obtain missingness-adjusted Wald ratio, two-stage least squares and inverse variance weighted estimates. The two methods are evaluated and compared in simulations, with results suggesting that they can both mitigate selection bias but may yield parameter estimates with large standard errors in some settings. In an illustrative real-data application, we investigate the effects of body mass index on smoking using data from the Avon Longitudinal Study of Parents and Children.

Exome sequencing of UK birth cohorts

Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights ranging from population genetics to applications across the social sciences. Here we present quality-controlled whole exome sequencing data from three UK birth cohorts: the Avon Longitudinal Study of Parents and Children (8,436 children and 3,215 parents), the Millenium Cohort Study (7,667 children and 6,925 parents) and Born in Bradford (8,784 children and 2,875 parents). The overall objective of this coordinated effort is to make the resulting high-quality data widely accessible to the global research community in a timely manner. We describe how the datasets were generated and subjected to quality control at the sample, variant and genotype level. We then present some preliminary analyses to illustrate the quality of the datasets and probe potential sources of bias. We introduce measures of ultra-rare variant burden to the variables available for researchers working on these cohorts, and show that the exome-wide burden of deleterious protein-truncating variants, S het burden, is associated with educational attainment and cognitive test scores. The whole exome sequence data from these birth cohorts (CRAM &amp; VCF files) are available through the European Genome-Phenome Archive, and here provide guidance for their use.

Climate change beliefs and behaviours: Data collected from 30-year-old offspring and their parents in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Climate change is causing a suite of environmental and social issues. Understanding patterns of climate change beliefs and behaviours, and the factors which shape these attitudes and actions, is therefore essential. This data note describes the novel data collection of climate belief and behaviour questions embedded within the Avon Longitudinal Study of Parents and Children (ALSPAC), a longitudinal population-based birth cohort in southwest England. Two generations of ALSPAC participants completed the questionnaires containing these climate questions: the Generation-1 (G1) offspring (n=4,341), Generation-0 (G0) mothers (n=4,793), and the G0 mother’s partners (n=2,111). The questions asked about: belief in climate change; concern over climate change; whether climate change is caused by human activity; whether individual behaviours can impact climate change; the impacts of climate change in the participants’ local area; and whether participants were engaging in any of 17 pro-environmental behaviours (e.g., recycling more, reducing meat/dairy consumption) for climate change and/or other reasons. The majority of participants believed the climate was definitely changing (~80%), were somewhat or very concerned about climate change (~90%) and attributed most or all of climate change to human activity (~75%), with only small differences between the generations. On average, participants reported engaging in between 5 and 6 actions because of concerns regarding climate change (5.8 in G0 mothers; 5.2 in G1 offspring and G0 partners). Associations with sociodemographic factors (e.g., age, sex, ethnicity and socioeconomic background) were relatively weak, but positive relationships between highest level of education and greater climate change belief, concern and behaviours were evident. Increased climate belief and concern also predicted engaging in more pro-environmental actions. Responses to these climate questions were more similar within-families. This data note provides important information for future users of these data, as well as discussing some of the key strengths, limitations and considerations for data users.

Immunometabolic Blood Biomarkers of Developmental Trajectories of Depressive Symptoms: Findings From the ALSPAC Birth Cohort.

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n=1709-3410); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n=2059 and n=2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n=2256). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (ORdepression=22.80, 95% CI 15.25-34.37; ORGAD=19.32, 95% CI 12.86-29.22) and adulthood-onset (ORdepression=7.68, 95% CI 5.31-11.17; ORGAD=5.39, 95% CI 3.65-7.94) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and intervention opportunities for adverse cardiometabolic profile in different groups of young people with depression.