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. 2022 Dec 20:11:e74320.
doi: 10.7554/eLife.74320.

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

Amanda M Hughes  1   2 , Eleanor Sanderson  1   2 , Tim Morris  1   2 , Ziada Ayorech  3   4 , Martin Tesli  5   6 , Helga Ask  3   5 , Ted Reichborn-Kjennerud  5   7 , Ole A Andreassen  6   7 , Per Magnus  8 , Øyvind Helgeland  9 , Stefan Johansson  10   11 , Pål Njølstad  12   13 , George Davey Smith  1   2 , Alexandra Havdahl #  1   2   3   4   5 , Laura D Howe #  1   2 , Neil M Davies #  1   2   14
Affiliations

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

Amanda M Hughes et al. Elife. .

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.

Keywords: MBRN; Mendelian randomization; MoBa; Within-family; body mass index; epidemiology; genetics; genomics; global health; human; within-families.

Plain language summary

Some studies show that children with obesity are more likely to receive a diagnosis of depression, anxiety, or attention-deficit hyperactivity disorder (ADHD). But this does not necessarily mean obesity causes these conditions. Depression, anxiety, or ADHD could cause obesity. A child's environment, including family income or their parents' mental health, could also affect a child's weight and mental health. Understanding the nature of these relationships could help scientists develop better interventions for both obesity and mental health conditions. Genetic studies may help scientists better understand the role of the environment in these conditions, but it's important to consider both the child's and their parents’ genetics in these analyses. This is because parents and children share not only genes, but also environmental conditions. For example, families that carry genetic variants associated with higher body weight might also have lower incomes, if parents have been affected by biases against heavier people in society and the workplace. Children in these families could have worse mental health because of effects of their parent’s weight, rather than their own weight. Looking at both child and adult genetics can help disentangle these processes. Hughes et al. show that a child's own body mass index, a ratio of weight and height, is not strongly associated with the child’s mental health symptoms. They analysed genetic, weight, and health survey data from about 41,000 8-year-old children and their parents. The results suggest that a child's own BMI does not have a large effect on their anxiety symptoms. There was also no clear evidence that a child's BMI affected their symptoms of depression or ADHD. These results contradict previous studies, which did not account for parental genetics. Hughes et al. suggest that, at least for eight-year-olds, factors linked with adult weight and which differ between families may be more critical to a child's mental health than a child’s own weight. For older children and adolescents, this may not be the case, and the individual’s own weight may be more important. As a result, policies designed to reduce obesity in mid-childhood are unlikely to greatly improve the mental health of children. On the other hand, policies targeting the environmental or societal factors contributing to higher body weights, bias against people with higher weights, and poor child mental health directly may be more beneficial.

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Conflict of interest statement

AH, ES, TM, ZA, MT, HA, TR, PM, ØH, SJ, PN, GD, AH, LH, ND No competing interests declared, OA has received speaker’s honorarium from Sunovion and Lundbeck and is a consultant for HealthLytix

Figures

Figure 1.
Figure 1.. Bias in Mendelian randomization studies which do not account for parental genotype.
Figure 1 is reproduced from Figure 1; Morris et al., 2020. Population stratification due to ancestral differences (yellow lines), dynastic effects (red lines), and assortative mating (green line). In within-family Mendelian randomization, parental genotype is controlled for, so effect estimates for the influence of child’s genotype on child phenotypes are unbiased by these processes.
Figure 2.
Figure 2.. BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for adult BMI (N=40,949 trios).
Coefficients represent standard-deviation change in outcomes per 5 kg/m2 increase in BMI, shown with 95% confidence intervals.
Figure 3.
Figure 3.. BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for childhood body size (N=40,949 trios).
Coefficients represent standard-deviation change in outcomes per 5 kg/m2 increase in BMI, shown with 95% confidence intervals.
Appendix 1—figure 1.
Appendix 1—figure 1.. Flow chart of inclusion and exclusion of MoBa participants into the study sample.
Appendix 1—figure 2.
Appendix 1—figure 2.. Associations of child’s BMI polygenic scores with ancestry.
Associations of the child’s polygenic scores for BMI and the child’s principal components of ancestry, adjusted for the child’s genotyping centre and chip.
Appendix 1—figure 3.
Appendix 1—figure 3.. Associations of child’s BMI polygenic scores with ancestry, adjusted for parental polygenic scores.
Associations of the child’s polygenic scores for BMI and the child’s principal components of ancestry, adjusted for the child’s genotyping centre and chip and the parents’ polygenic scores.
See this image and copyright information in PMC

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