Dataset Information

Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study.

ABSTRACT:

Background

Higher BMI in childhood is associated with emotional and behavioural problems, but these associations may not be causal. Results of previous genetic studies imply causal effects but may reflect influence of demography and the family environment.

Methods

This study used data on 40,949 8-year-old children and their parents from the Norwegian Mother, Father and Child Cohort Study (MoBa) and Medical Birth Registry of Norway (MBRN). We investigated the impact of BMI on symptoms of depression, anxiety, and attention-deficit hyperactivity disorder (ADHD) at age 8. We applied within-family Mendelian randomization, which accounts for familial effects by controlling for parental genotype.

Results

Within-family Mendelian randomization estimates using genetic variants associated with BMI in adults suggested that a child's own BMI increased their depressive symptoms (per 5 kg/m² increase in BMI, beta = 0.26 S.D., CI = -0.01,0.52, p=0.06) and ADHD symptoms (beta = 0.38 S.D., CI = 0.09,0.63, p=0.009). These estimates also suggested maternal BMI, or related factors, may independently affect a child's depressive symptoms (per 5 kg/m² increase in maternal BMI, beta = 0.11 S.D., CI:0.02,0.09, p=0.01). However, within-family Mendelian randomization using genetic variants associated with retrospectively-reported childhood body size did not support an impact of BMI on these outcomes. There was little evidence from any estimate that the parents' BMI affected the child's ADHD symptoms, or that the child's or parents' BMI affected the child's anxiety symptoms.

Conclusions

We found inconsistent evidence that a child's BMI affected their depressive and ADHD symptoms, and little evidence that a child's BMI affected their anxiety symptoms. There was limited evidence of an influence of parents' BMI. Genetic studies in samples of unrelated individuals, or using genetic variants associated with adult BMI, may have overestimated the causal effects of a child's own BMI.

Funding

This research was funded by the Health Foundation. It is part of the HARVEST collaboration, supported by the Research Council of Norway. Individual co-author funding: the European Research Council, the South-Eastern Norway Regional Health Authority, the Research Council of Norway, Helse Vest, the Novo Nordisk Foundation, the University of Bergen, the South-Eastern Norway Regional Health Authority, the Trond Mohn Foundation, the Western Norway Regional Health Authority, the Norwegian Diabetes Association, the UK Medical Research Council. The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit.

SUBMITTER: Hughes AM

PROVIDER: S-EPMC9767454 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study.

Hughes Amanda M AM Sanderson Eleanor E Morris Tim T Ayorech Ziada Z Tesli Martin M Ask Helga H Reichborn-Kjennerud Ted T Andreassen Ole A OA Magnus Per P Helgeland Øyvind Ø Johansson Stefan S Njølstad Pål P Davey Smith George G Havdahl Alexandra A Howe Laura D LD Davies Neil M NM

eLife 20221220

<h4>Background</h4>Higher BMI in childhood is associated with emotional and behavioural problems, but these associations may not be causal. Results of previous genetic studies imply causal effects but may reflect influence of demography and the family environment.<h4>Methods</h4>This study used data on 40,949 8-year-old children and their parents from the Norwegian Mother, Father and Child Cohort Study (MoBa) and Medical Birth Registry of Norway (MBRN). We investigated the impact of BMI on sympt ...[more]

PMID: 36537070

Similar Datasets

Project description:BackgroundChildren with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms.MethodsInfants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24 and 38 months, and 7 years of age. Symptoms of ASD, ADHD and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations.ResultsIncreased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became nonsignificant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal.ConclusionsThe specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders.

Project description:BackgroundIn some observational studies, attention-deficit/hyperactivity disorder has been linked to allergic diseases, but the findings are debatable. This study aimed to determine whether attention-deficit/hyperactivity disorder (ADHD) is causally related to allergic asthma, allergic rhinitis, pollen allergy, allergic urticaria, and allergic conjunctivitis using the two-sample Mendelian Randomization (MR) approach.MethodsWe did a two-sample Mendelian randomization (MR) study, which chose single nucleotide polymorphisms (SNPs) that are highly associated with attention-deficit/hyperactivity disorder (ADHD) levels from the Psychiatric Genomics Consortium (PGC) on 20,183 cases and 35,191 controls as our instruments. Outcomes datasets included genome-wide association study (GWAS) meta-analysis (n = 1,415,804). The summary statistics of outcome data were obtained from the FinnGen datasets including allergic asthma (10,877 cases and 180,942 controls), allergic rhinitis (8,430 cases and 298,829 controls), pollen allergy (4555cases and 301,734 controls), allergic urticaria (1792 cases and 299,491 controls) and allergic conjunctivitis (15,567 cases and 293,587 controls). Inverse variance weighted, MR-Egger, weighted median, were used to estimate the causal association between ADHD and allergic diseases. Cochran's Q test was used to quantify the heterogeneity of instrumental variables. MR-Egger intercept test, leave-one-out analysis, and the funnel plot were all used in sensitivity analyses.ResultsThe Mendelian randomization (MR) analysis indicated that ADHD in inverse variance weighted [odds ratio (OR) = 1.0612; 95% confidence interval (CI):1.0192-1.1049; p = 0.0039] lightly increased the risk of allergic asthma. In MR sensitivity analyses of the weighted median, a similar association was found. But no evidence for an effect of ADHD on allergic asthma risk was found in additional methods: MR-Egger (OR = 0.9592, 95% CI: 0.8384-1.0974, p = 0.5457), and weighted median (OR: =1.0341, 95% CI: 0.9785-1.0929, p = 0.2330). Also, no strong evidence for an effect of ADHD on other allergic diseases (allergic rhinitis, pollen allergy, allergic urticaria, and allergic conjunctivitis) incidence was found using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression.ConclusionAlthough several studies have found a link between ADHD and allergic diseases, our findings do not support that ADHD could increase allergic diseases incidence. Randomized controlled trials or Mendelian randomization studies with larger samples are still needed to draw more precise conclusions.

Project description:BackgroundObservational studies have found Attention Deficit Hyperactivity Disorder (ADHD) to be associated with an increased risk of adverse outcomes as well as with early risk factors; however it is not clear whether these associations reflect causal effects. Alternatives to traditional observational studies are needed to investigate causality: one such design is Mendelian randomization (MR), which uses genetic variants as instrumental variables for the exposure.MethodsIn this review we summarise findings from approximately 50 studies using MR to examine potentially causal associations with ADHD as either an exposure or outcome.ResultsTo-date, few MR ADHD studies have investigated causal evidence with other neurodevelopmental, mental health and neurodegenerative conditions but those that have suggest a complex relationship with autism, some evidence of a causal effect on depression and limited evidence of a causal effect on neurodegenerative conditions. For substance use, MR studies provide evidence consistent with a causal effect of ADHD on smoking initiation, but findings for other smoking behaviours and cannabis use are less consistent. Studies of physical health suggest bidirectional causal effects with higher body mass index, with stronger effects for childhood obesity, as well as some evidence of causal effects on coronary artery disease and stroke in adults and limited evidence of causal effects on other physical health problems or sleep. Studies suggest bidirectional relationships between ADHD and socio-economic markers and provide some evidence that low birthweight may be a causal risk factor for ADHD, while bidirectional evidence has been found for some environmental factors. Finally, there is emerging evidence of bidirectional causal links between ADHD genetic liability and biological markers of human metabolism and inflammation.ConclusionsWhile MR has advantages over traditional observational designs in addressing causality, we discuss limitations of current ADHD studies and future directions, including the need for larger genome-wide association studies (and using samples of different ancestries), and for triangulation with different methods.

Project description:Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits. We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD, we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results. Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta = -0.058, 95% CrI = (-0.072, -0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (-0.048, -0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively]. Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories.

Project description:Previous research has suggested a link between gut microbiota and attention deficit hyperactivity disorder (ADHD), but their causal relationship has not been elucidated. Aiming to comprehensively investigate their causal relationship and to identify specific causal microbe taxa for ADHD, we conducted a two-sample Mendelian randomization (MR) analysis. Instrumental variables of 211 gut microbiota taxa were obtained from gene wide association study (GWAS), and Mendelian randomization study was carried out to estimate their effects on ADHD risk from PGC GWAS (20,183 ADHD cases and 35,191 controls) and FinnGen GWAS (830 ADHD cases and 215,763 controls). Wald ratio (WR), inverse variance weighted (IVW), MR-Egger, and weighted median were the main methods to analyze causality, and MR results are verified by several sensitivity analysis analyses. At locus-wide significance level (p < 1 × 10-5), IVW results confirmed that genus Eubacteriumhalliigroup (p = 0.013) and genus RuminococcaceaeUCG013 (p = 0.049) were correlated with the risk of ADHD and genus Butyricicoccus (p = 0.009), genus Roseburia (p = 0.009), genus Desulfovibrio (p = 0.015), genus LachnospiraceaeNC2004group (p = 0.026), genus Romboutsia (p = 0.028) and family Oxalobacteraceae (p = 0.048) were protective factors of ADHD. Weighted median results indicated that genus Butyricicoccus (p = 0.018) was negatively correlated with the risk of ADHD. At genome-wide statistical significance level (p < 5 × 10-8), Wald ratio results demonstrated that genus Ruminococcustorquesgroup (p = 0.003) was a risk factor for ADHD, while genus Romboutsia (p = 0.006) and family Peptostreptococcaceae (p = 0.006) had a negative correlation with the risk of ADHD. In reverse MR analysis, IVW results showed that ADHD may lead to an increase in the abundance of genus Roseburia (p = 0.020). Analysis of heterogeneity (p > 0.05) and pleiotropy (p > 0.05) confirmed the robustness of MR results. We demonstrated that there was a potential causal relationship between gut microbiota and ADHD. Our research provides a foundation for understanding the causal relationship between gut microbiota and ADHD, and the several gut bacteria found in this study that may reduce the occurrence of ADHD may have potential in the prevention and treatment of ADHD.

Project description:BackgroundImmune system modulation has been shown to have a significant impact on attention deficit hyperactivity disorder (ADHD). Mendelian randomization (MR) analysis was used in this study to investigate the potential role of different immune cells in the development of ADHD to provide therapy and preventative alternatives.MethodsIn this study, 731 immune cells and the risk of ADHD were examined using publicly accessible genetic data and a two-sample MR analysis. Included were four different types of immunological profiles: determinate cells (DC), proportional cells (PC), median brightness level (MBL), and morphological characteristics (MA). It was discovered that single-nucleotide polymorphisms (SNPs) are linked to ADHD. To evaluate the dependability of the results, we conducted sensitivity analysis (heterogeneity and pleiotropy) and employed supplementary MR techniques, such as the inverse variance weighted (IVW) and MR-Egger. Graphs are used to display the final findings of the pertinent analyses.ResultsFollowing MR analysis, immune cells associated with a few low p value phenotypes may influence ADHD, and these immune cells may serve as an inspiration for clinical treatment practices that aim to prevent and cure ADHD. Immune cell phenotypes that may both increase and worsen the likelihood of having ADHD were identified by IVW results. These included CD27 on memory B cells (OR = 1.066, 95% CI = 1.024-1.109, p = 2E-3) and CD27 on IgD-CD38- (OR = 1.059, 95% CI = 1.018-1.103, p = 5E-3), among others. Immune cell phenotypes that may act as a safeguard against ADHD included CD3 on resting Treg (OR = 0.925, 95% CI = 0.888-0.963, p = 1.5E-4) and SSC-A on monocytes (OR = 0.951, 95% CI = 0.924-0.980, p = 8.5E-4), among others. The primary findings and the outcomes of the sensitivity analysis matched.ConclusionsThis study provides a broad theoretical foundation for the development of immune-oriented therapeutic strategies in future clinical practice by demonstrating a potential genetic relationship between immune cells and ADHD. This study also advances our understanding of how to use the immune pathway to prevent and treat ADHD.

Dataset Information

Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study.

Background

Methods

Results

Conclusions

Funding

Publications

Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets