The impact of anorexia nervosa and BMI polygenic risk on childhood growth: A 20-year longitudinal population-based study.

Growth deviating from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGSs) for AN and BMI are associated with growth trajectories spanning the first two decades of life. AN PGSs and BMI PGSs were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 8,654). Using generalized (mixed) linear models, we associated PGSs with trajectories of weight, height, body mass index (BMI), fat mass index (FMI), lean mass index (LMI), and bone mineral density (BMD). Female participants with AN PGSs one standard deviation (SD) higher had, on average, 0.004% slower growth in BMI between the ages 6.5 and 24 years and a 0.4% slower gain in BMD between the ages 10 and 24 years. Higher BMI PGSs were associated with faster growth for BMI, FMI, LMI, BMD, and weight trajectories in both sexes throughout childhood. Female participants with both a high AN PGS and a low BMI PGS showed slower growth compared to those with both a low AN PGS and a low BMI PGS. We conclude that AN PGSs and BMI PGSs have detectable sex-specific effects on growth trajectories. Female participants with a high AN PGS and low BMI PGS likely constitute a high-risk group for AN, as their growth was slower compared to their peers with high PGSs on both traits. Further research is needed to better understand how the AN PGS and the BMI PGS co-influence growth during childhood and whether a high BMI PGS can mitigate the effects of a high AN PGS.

Associations of childhood diet quality scores with arterial stiffness and carotid artery intima-media thickness in adolescence/early adulthood: findings from the ALSPAC cohort.

This study examined the relationship between childhood diet quality and arterial stiffness and thickness during adolescence/early adulthood. Participants were from the Avon Longitudinal Study of Parents and Children (ALSPAC) with dietary data at ages 7, 10 and 13 years and pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) at ages 17 and/or 24 years. Diet quality (DQ) was assessed using five scores: a children's Mediterranean-style diet (C-rMED) Z-score, a children's Dietary Inflammatory Z-score (C-DIS), a DASH diet Z-score, a children's Eatwell Guide (C-EWG) Z-score reflecting UK dietary guidelines and a data-driven obesogenic Z-score. Adjusted regression models examined the associations between DQ scores at 7-13 years and PWV and cIMT at 17 and 24 years. In adjusted models, a high v. low Obesogenic Z-score at 7 and 10 years was associated with higher PWV at 17: ß 0.07 (95 % CI 0.01, 0.13) and ß 0.10 (95 % CI 0.04, 0.16), respectively. A high v. low C-rMED Z-score at 7 years was associated with lower PWV at 17 (ß -0.07; 95 % CI -0.14, -0.01). A high (more anti-inflammatory) vs low C-DIS Z-score at 10 years was associated with a lower PWV at 17 years: ß -0.06 (95 % CI -0.12, -0.01). No other associations were observed. In conclusion, an Obesogenic dietary pattern in childhood (7-10 years) was related to increased arterial stiffness, while Mediterranean-style and anti-inflammatory diets were related to decreased arterial stiffness in adolescence. This highlights the importance of establishing healthy dietary habits early in life to protect against vascular damage.

Genetic risk for schizophrenia is associated with increased proportion of indirect connections in brain networks revealed by a semi-metric analysis: evidence from population sample stratified for polygenic risk.

Research studies based on tractography have revealed a prominent reduction of asymmetry in some key white-matter tracts in schizophrenia (SCZ). However, we know little about the influence of common genetic risk factors for SCZ on the efficiency of routing on structural brain networks (SBNs). Here, we use a novel recall-by-genotype approach, where we sample young adults from a population-based cohort (ALSPAC:N genotyped = 8,365) based on their burden of common SCZ risk alleles as defined by polygenic risk score (PRS). We compared 181 individuals at extremes of low (N = 91) or high (N = 90) SCZ-PRS under a robust diffusion MRI-based graph theoretical SBN framework. We applied a semi-metric analysis revealing higher SMR values for the high SCZ-PRS group compared with the low SCZ-PRS group in the left hemisphere. Furthermore, a hemispheric asymmetry index showed a higher leftward preponderance of indirect connections for the high SCZ-PRS group compared with the low SCZ-PRS group (PFDR < 0.05). These findings might indicate less efficient structural connectivity in the higher genetic risk group. This is the first study in a population-based sample that reveals differences in the efficiency of SBNs associated with common genetic risk variants for SCZ.

Childhood Gender Nonconformity and Parental Maltreatment as Mediators of Sexual Orientation Disparities in Childhood Emotional and Behavioral Difficulties.

The mechanisms underlying sexual orientation differences in psychopathology originating in childhood remain understudied since sexual orientation does not directly manifest in childhood. This study tested whether childhood gender nonconformity and parental maltreatment before age 6 years 9 months partly explained sexual orientation disparities in the developmental trajectories of emotional and behavioral difficulties from age 6 years 9 months to 11 years 8 months. The Avon Longitudinal Study of Parents and Children was used (2182 boys and 2422 girls, Mage = 15.5, 90% White). After controlling for early life factors, non-heterosexual boys and girls displayed significantly greater emotional and behavioral difficulties than their heterosexual counterparts at all three ages. There was a sex difference in the mediating effects. For girls, sexual orientation disparities in childhood emotional and behavioral difficulties were partially explained by childhood gender nonconformity. For boys, sexual orientation disparities in childhood emotional and behavioral difficulties were partially explained by a path through greater childhood gender nonconformity, leading to increased risk of being the targets of parental maltreatment. Childhood gender nonconformity, parental maltreatment, and other early life factors only partially explain sexual orientation disparities in childhood emotional and behavioral difficulties. The mediating effects of childhood gender nonconformity and parental maltreatment on the association between sexual orientation and childhood emotional and behavioral difficulties differ between the sexes.

The dietary approaches to stop hypertension (DASH) dietary pattern in childhood in relation to cardiometabolic risk in adolescence and early adulthood in the ALSPAC birth cohort.

OBJECTIVE: To investigate the relationship between the dietary approaches to stop hypertension (DASH)-style dietary patterns in childhood and cardiometabolic risk (CMR) in adolescence/early adulthood. DESIGN: Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort. Diet diary data collected at 7, 10 and 13 years were used to calculate DASH-style diet scores (DDS). Multivariable linear regression models were used to investigate the associations between the DDS at 7, 10 and 13 years and CMR scores, calculated at 17 and 24 years. SETTING: The ALSPAC cohort included children born in south-west England in 1991-1992. PARTICIPANTS: Children with complete dietary, covariate and cardiometabolic data at 17 (n 1,526) and 24 years (n 1,524). RESULTS: A higher DDS at 7 and 10 years was negatively associated with CMR scores at 17 years (ß = -0·64 (95 % CI -1·27, -0·006), Ptrend=0·027 for fifth v. first DDS quintile at 7 years; ß = -0·73 (95 % CI -1·35, -0·12) and Ptrend=0·037 for fifth v. first DDS quintile at 10 years) and at 24 years (ß = -0·92 (95 % CI -1·49, -0·34) Ptrend = 0·001 for fifth v. first DDS quintile at 7 years; ß = -0·60 (95 % CI -1·20, -0·05) Ptrend = 0·092 for fifth v. first DDS quintile at 10 years). No associations were found between the DDS at 13 years and CMR score at 17 and 24 years. CONCLUSION: Greater adherence with a DASH-style diet during childhood was associated with better cardiometabolic health in adolescence/adulthood in the ALSPAC cohort. The components of the DASH diet could be recommended to improve children's cardiometabolic health.

Use of Correct and Incorrect Methods of Accounting for Age in Studies of Epigenetic Accelerated Aging: Implications and Recommendations for Best Practices.

Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic "clocks" (which estimate age via DNA methylation (DNAm) patterns), we report on 3 different approaches in the epidemiologic literature-1 incorrect and 2 correct-on the treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%) or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introduced by use of the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias towards the null, and we discuss implications for extant research and recommendations for best practices.

Relative age in the school year and risk of mental health problems in childhood, adolescence and young adulthood.

PURPOSE: Relative age within the school year ('relative age') is associated with increased rates of symptoms and diagnoses of mental health disorders, including ADHD. We aimed to investigate how relative age influences mental health and behaviour before, during and after school (age range: 4-25 years). METHOD: We used a regression discontinuity design to examine the effect of relative age on risk of mental health problems using data from a large UK population-based cohort (Avon Longitudinal Study of Parents and Children (ALSPAC); N = 14,643). We compared risk of mental health problems between ages 4 and 25 years using the parent-rated Strengths and Difficulties Questionnaire (SDQ), and depression using self-rated and parent-rated Short Mood and Feelings Questionnaire (SMFQ) by relative age. RESULTS: The youngest children in the school year have greater parent-rated risk of mental health problems, measured using parent-rated SDQ total difficulties scores. We found no evidence of differences before school entry [estimated standardised mean difference (SMD) between those born on 31 August and 1 September: .02 (-.05, .08)]. We found that estimates of effect size for a 1-year difference in relative age were greatest at 11 years [SMD: .22 (.15, .29)], but attenuated to the null at 25 years [SMD: -.02 (-.11, .07)]. We did not find consistent evidence of differences in self-rated and parent-rated depression by relative age. CONCLUSIONS: Younger relative age is associated with poorer parent-rated general mental health, but not symptoms of depression.

Adherence to UK dietary guidelines in school-aged children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

Compliance to UK dietary recommendations was assessed in school-aged children from a population-based cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). A Children's Eatwell Guide (C-EWG) score was developed to assess socio-demographic predictors of meeting dietary recommendations. ALSPAC children with plausible diet diary data at 7 years (n 5373), 10 years (n 4450) and 13 years (n 2223) were included in the study. Their dietary intakes (recorded between 1998 and 2006) were compared with dietary guidelines for total and saturated fats, free sugars, salt, fibre, protein, carbohydrates, fruit and vegetables, non-oily and oily fish and red/processed meat. The C-EWG score (0-9 points) indicated the number of recommendations met at each age. Cross-sectional associations between socio-demographic characteristics and C-EWG scores were assessed using multivariable regression. The lowest adherence to guidelines at 7 years was for sugar (0·1 % meeting recommendations), followed by fibre (7·7 %), oily fish (9·5 %), saturated fat (9·7 %) and fruit and vegetables (15·2 %). Highest adherence was for limiting red/processed meat (67·3 %) and meeting carbohydrate recommendations (77·3 %). At 7 years, 12·1 % of participants failed to meet any of the nine recommendations, 26·9 % met one and 28·2 % met two. Similar patterns were seen at 10 and 13 years. A lower social class and maternal educational attainment and higher maternal BMI were associated with meeting fewer recommendations. Most school-aged children in this cohort did not meet UK dietary recommendations, particularly children from lower socio-economic backgrounds. Additional public health initiatives are needed to improve the quality of UK children's diets, particularly targeting lower socio-economic groups.

Prospective association between adherence to UK dietary guidelines in school-age children and cardiometabolic risk markers in adolescence/early adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

Research into how alignment to UK dietary guidelines during childhood affects cardiometabolic health is limited. The association between adherence to UK dietary guidelines during childhood and overall cardiometabolic risk (CMR) in adolescence/early adulthood was explored using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC children with diet diaries completed at 7, 10 and 13 years of age, and data on CMR markers at 17 years (n 1940) and 24 years (n 1957) were included. A children's Eatwell Guide (C-EWG) score was created by comparing dietary intakes at each age to UK dietary guidelines for nine foods/nutrients. Cardiometabolic health at 17 and 24 years was assessed using a composite CMR score. Multivariable linear regression models examined associations between C-EWG scores at 7, 10 and 13 years and the CMR score at 17 and 24 years, adjusting for confounders. C-EWG scores were generally low. However, a higher score (adherence to more dietary guidelines) at 7 years old was associated with a lower CMR score at 17 and 24 years: ß -0·13 (95 % CI -0·25, -0·01) and ß -0·25 (95 % CI -0·38, -0·13) for a 1-point increase in C-EWG score, respectively. A higher C-EWG score at 10 years was also associated with a lower CMR z-score at 24 years. No clear associations were evident at other ages. Greater adherence to UK dietary guidelines during mid-childhood was associated with a better overall cardiometabolic profile, suggesting that encouraging children to eat in this way has long-term benefits to health.

Is there an association between physical activity and lower urinary tract symptoms in adolescent girls? Results from the Avon Longitudinal Study of Parents and Children.

INTRODUCTION AND HYPOTHESIS: Lower urinary tract symptoms (LUTS) are common among adolescent girls. Physical activity (PA) has been implicated as both a risk (high-impact PA) and protective factor (low-impact, moderate to vigorous intensity PA) for LUTS in adult women, but its role in adolescent girls is unclear. This study investigated the prospective association between physical activity and LUTS risk in adolescent girls. METHODS: The sample comprised 3,484 female participants in the Avon Longitudinal Study of Parents and Children. Multivariate logistic regression models were used to examine daily minutes of moderate to vigorous PA (MVPA) at ages 11 and 15 years in relation to LUTS at ages 14 and 19 respectively. MVPA was assessed by 7-day accelerometer data. LUTS were assessed by questionnaire. MVPA were analyzed as continuous (minutes/day) and categorical variables (<10th percentile, 10-89th percentile, ≥90th percentile). RESULTS: Prevalence of LUTS ranged from 2.0% for bedwetting to 9.5% for nocturia at age 14 and from 2.0% for straining to urinate to 35.5% for interrupted urine flow at age 19. Physical activity was not associated with LUTS at either time-point. CONCLUSIONS: Given the prevalence of LUTS in female adolescent populations, although this study did not find an association with accelerometer-measured MVPA, other aspects of PA that may serve as risk or protective factors deserve investigation.

Maternal postnatal depression and anxiety and the risk for mental health disorders in adolescent offspring: Findings from the Avon Longitudinal Study of Parents and Children cohort.

OBJECTIVE: The impacts of postnatal psychiatric disorders on different types of mental health problems in offspring are unclear. We investigated the prospective associations of maternal postnatal depression, and anxiety, with offspring depression, anxiety, psychotic-like experiences and Borderline Personality Disorder symptoms, in adolescence, and examined whether these were independent of each other. METHODS: Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Maternal postnatal depression and anxiety at 8 weeks were measured using the Edinburgh Postnatal Depression Scale and Crown-Crisp Index, respectively. Offspring mental health outcomes were measured at 10-13 years old, using a variety of questionnaire-based and interview assessments. Logistic regression analyses were used to assess the associations between maternal postnatal risk factors and offspring mental health, and path analysis was used to investigate the pathways of maternal postnatal factors to adolescent offspring outcomes. RESULTS: Data were available for 14,054 mothers with information reported on postnatal depression and 13,892 on postnatal anxiety. Logistic regression analyses found significant associations between maternal postnatal depression and offspring anxiety at 10 years old (odds ratio = 1.039, 95% confidence interval = [1.005, 1.073], p = 0.022) and between maternal postnatal anxiety and offspring psychotic experiences at 12/13 years old (odds ratio = 1.042, 95% confidence interval = [1.008, 1.077], p = 0.016). These significant associations remained after applying path analyses, when we controlled for potential offspring psychopathological overlay. CONCLUSION: These findings suggest that mothers with postnatal depression are more likely to have offspring with anxiety at 10 years old, and that mothers with postnatal anxiety are more likely to have offspring with psychotic experiences at 12/13 years old. Our findings suggest specific pathways in the association between postnatal anxiety/depression and offspring mental health and contribute to the importance of identifying mothers and their offspring with increased vulnerability to adverse outcomes resulting from postnatal mental health disorders.

Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children.

Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics. We investigated whether polygenic risk score (PRS) of TS and pregnancy-related factors together enhance the explained variance of tic occurrence in the Avon Longitudinal Study of Parents and Children (Ncases  = 612; Ncontrols  = 4,201; 50% male; mean age 13.8 years). We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible joint effects of genetic and pregnancy-related risk factors using a multivariable approach, and explored mediation effects between the pregnancy-related risk factors in explaining tic presence. The PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression explained significantly more variance of tic presence compared to models including only the PRS. Furthermore, we found that the cumulative adverse pregnancy risk score mediated the association between several pregnancy-related factors (maternal anxiety, depression, and smoking) and tics. The combination of a PRS and pregnancy-related risk factors explained more variance of tics in a general population cohort compared to studying these factors in isolation.

Testing Deprivation and Threat: A Preregistered Network Analysis of the Dimensions of Early Adversity.

Despite abundant evidence of the detrimental effects of childhood adversity, its nature and underlying mechanisms remain contested. One influential theory, the dimensional model of adversity and psychopathology, proposes deprivation and threat as distinct dimensions of early experience. In this preregistered analysis of data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we used a network and clustering approach to assess the dimensionality of relationships between childhood adversity and adolescent cognition and emotional functioning, and we used recursive partitioning to identify timing effects. We found evidence that deprivation and threat are separate dimensions of adversity and that early experiences of deprivation cluster with later measures of cognition and emotional functioning. This cluster varies by age of exposure; it includes fewer forms of deprivation as children grow from infancy to middle childhood. Our measures did not form a specific cluster linking threat to emotional functioning.

Evaluating future risk of NAFLD in adolescents: a prediction and decision curve analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex. METHODS: Aged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed "routine clinical measures". Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1. RESULTS: The "routine clinical measures" model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The "routine clinical measures" model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents' assumption, was the "routine clinical measures" model. However, the net benefit was marginal (0.0054 [0.0034-0.0075]). CONCLUSION: In adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level.

Mode of delivery and maternal sexual wellbeing: A longitudinal study.

OBJECTIVES: To investigate the association between mode of delivery and subsequent maternal sexual wellbeing. DESIGN: Prospective birth cohort study. SETTING: Avon (in Bristol area), UK. POPULATION: Participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: Mode of delivery was abstracted from obstetric records and sexual wellbeing measures were collected via a self-report questionnaire. Missing data were imputed using multiple imputation, and ordinal logistic regression models for ordered categorical outcomes were adjusted for the covariates maternal age at delivery, pre-pregnancy body mass index, diabetes during pregnancy, socio-economic position, parity, depression and anxiety. MAIN OUTCOME MEASURES: Sexual enjoyment and frequency at four time points postpartum (between 33 months and 18 years) and two types of sex-related pain (pain in the vagina during sex and elsewhere after sex) at 11 years postpartum. RESULTS: We found no association between mode of delivery and sexual enjoyment (e.g. adjusted odds ratio [OR] 1.11, 95% confidence interval [95% CI] 0.97-1.27 at 33 months) or sexual frequency (OR 0.99, 95% CI 0.88-1.12 at 33 months). Caesarean section was associated with an increased odds of pain in the vagina during sex at 11 years postpartum as compared with vaginal delivery in the adjusted model (OR 1.74, 95% CI 1.46-2.08). CONCLUSIONS: These findings provide no evidence supporting associations between caesarean section and sexual enjoyment or frequency. However, mode of delivery was shown to be associated with dyspareunia, which may not be limited to abdominal scarring.

The inflammatory potential of the diet in childhood is associated with cardiometabolic risk in adolescence/young adulthood in the ALSPAC birth cohort.

PURPOSE: This study examined the association between a Dietary Inflammatory Score adapted for children (cDIS) and Cardiometabolic Risk (CMR) score in adolescence/early adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: The cDIS was calculated at 7, 10 and 13 years using diet diary data. Anthropometric and biochemical data at 17 (N = 1937) and 24 (N = 1957) years were used to calculate CMR scores at each age [mean sex-specific z-scores from triacylglycerol, HDL-cholesterol, LDL-cholesterol, mean arterial blood pressure (MAP), homeostatic model assessment of insulin resistance (HOMA-IR) and fat-mass index (FMI)]. Multivariable linear regression models examined associations between cDIS at 7, 10 and 13 years and a continuous CMR z-score and individual CMR markers at 17 and 24 years. RESULTS: In fully adjusted models, a higher cDIS (more pro-inflammatory diet) at 7 years was associated with an increase in CMR z-score at 17 years (ß 0.19; 95% CI 0.03-0.35 for third versus first cDIS tertile) and at 24 years (ß 0.28; 95% CI 0.11,0.44 for third versus first cDIS tertile). There was a weak association between a higher cDIS at 10 years and an increase in CMR z-score at 17 years (ß 0.16; 95% CI - 0.003, 0.32 for third versus first cDIS tertile). No other clear associations were evident. FMI, MAP and HOMA-IR were the main CMR factors contributing to these associations. CONCLUSION: A more pro-inflammatory diet during childhood was associated with a worse cardiometabolic profile in late adolescence/early adulthood. A childhood diet abundant in nutrients with anti-inflammatory properties could help reduce development of CMR factors.

Eating disorder symptoms and their associations with anthropometric and psychiatric polygenic scores.

BACKGROUND: Eating disorder (ED) symptoms are prevalent in the general population, but their shared genetic underpinnings with psychiatric, metabolic, and anthropometric traits are not known. Here, we examined if polygenic scores (PGSs) of traits associated with anorexia nervosa are also associated with adolescent ED symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: A total of 8654 participants with genotype data and at least one phenotypic measure were included from the ALSPAC study. We associated PGS from 25 traits (16 psychiatric, 4 metabolic, and 5 anthropometric) with eight ED symptoms, including behaviours such as fasting for weight loss and cognitions such as body dissatisfaction. RESULTS: Higher attention deficit hyperactivity disorder PGS and lower educational attainment PGS were associated with fasting for weight loss. Higher insomnia PGS was associated with increased body dissatisfaction. We found no evidence of an association between metabolic trait PGS and any ED symptom. Fat-free mass, fat mass, and body fat percentage PGSs, were positively associated with binge eating, excessive exercise, fasting for weight loss, body dissatisfaction, and weight and shape concern. CONCLUSIONS: ED symptoms are genetically associated with psychiatric and anthropometric, but not with metabolic traits. Our findings provide insights for future genetic research investigating on why some individuals with ED symptoms progress to develop threshold EDs while others do not.

A Structured Approach to Evaluating Life-Course Hypotheses: Moving Beyond Analyses of Exposed Versus Unexposed in the -Omics Context.

The structured life-course modeling approach (SLCMA) is a theory-driven analytical method that empirically compares multiple prespecified life-course hypotheses characterizing time-dependent exposure-outcome relationships to determine which theory best fits the observed data. In this study, we performed simulations and empirical analyses to evaluate the performance of the SLCMA when applied to genomewide DNA methylation (DNAm). Using simulations (n = 700), we compared 5 statistical inference tests used with SLCMA, assessing the familywise error rate, statistical power, and confidence interval coverage to determine whether inference based on these tests was valid in the presence of substantial multiple testing and small effects-2 hallmark challenges of inference from -omics data. In the empirical analyses (n = 703), we evaluated the time-dependent relationship between childhood abuse and genomewide DNAm. In simulations, selective inference and the max-|t|-test performed best: Both controlled the familywise error rate and yielded moderate statistical power. Empirical analyses using SLCMA revealed time-dependent effects of childhood abuse on DNAm. Our findings show that SLCMA, applied and interpreted appropriately, can be used in high-throughput settings to examine time-dependent effects underlying exposure-outcome relationships over the life course. We provide recommendations for applying the SLCMA in -omics settings and encourage researchers to move beyond analyses of exposed versus unexposed individuals.

Combining Longitudinal Data From Different Cohorts to Examine the Life-Course Trajectory.

Longitudinal data are necessary to reveal changes within an individual as he or she ages. However, rarely will a single cohort study capture data throughout a person's entire life span. Here we describe in detail the steps needed to develop life-course trajectories from cohort studies that cover different and overlapping periods of life. Such independent studies are probably from heterogenous populations, which raises several challenges, including: 1) data harmonization (deriving new harmonized variables from differently measured variables by identifying common elements across all studies); 2) systematically missing data (variables not measured are missing for all participants in a cohort); and 3) model selection with differing age ranges and measurement schedules. We illustrate how to overcome these challenges using an example which examines the associations of parental education, sex, and race/ethnicity with children's weight trajectories. Data were obtained from 5 prospective cohort studies (carried out in Belarus and 4 regions of the United Kingdom) spanning data collected from birth to early adulthood during differing calendar periods (1936-1964, 1972-1979, 1990-2012, 1996-2016, and 2007-2015). Key strengths of our approach include modeling of trajectories over wide age ranges, sharing of information across studies, and direct comparison of the same parts of the life course in different geographical regions and time periods. We also introduce a novel approach of imputing individual-level covariates of a multilevel model with a nonlinear growth trajectory and interactions.

Precursors and correlates of transient and persistent longitudinal profiles of psychotic experiences from late childhood through early adulthood.

BACKGROUND: Psychotic experiences are reported by 5-10% of young people, although only a minority persist and develop into psychotic disorders. It is unclear what characteristics differentiate those with transient psychotic experiences from those with persistent psychotic experiences that are more likely to be of clinical relevance. AIMS: To investigate how longitudinal profiles of psychotic experiences, created from assessments at three different time points, are influenced by early life and co-occurring factors. METHOD: Using data from 8045 individuals from a birth cohort study, longitudinal profiles of psychotic experiences based on semi-structured interviews conducted at 12, 18 and 24 years were defined. Environmental, cognitive, psychopathological and genetic determinants of these profiles were investigated, along with concurrent changes in psychopathology and cognition. RESULTS: Following multiple imputations, the distribution of longitudinal profiles of psychotic experiences was none (65.7%), transient (24.1%), low-frequency persistent (8.4%) and high-frequency persistent (1.7%). Individuals with high-frequency persistent psychotic experiences were more likely to report traumatic experiences, other psychopathology, a more externalised locus of control, reduced emotional stability and conscientious personality traits in childhood, compared with those with transient psychotic experiences. These characteristics also differed between those who had any psychotic experiences and those who did not. CONCLUSIONS: These findings indicate that the same risk factors are associated with incidence as with persistence of psychotic experiences. Thus, it might be that the severity of exposure, rather than the presence of specific disease-modifying factors, is most likely to determine whether psychotic experiences are transient or persist, and potentially develop into a clinical disorder over time.