体质指数与儿童期抑郁、焦虑和注意缺陷多动障碍症状:基于家系的孟德尔随机化研究。
Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study.
机构信息
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, United Kingdom.
出版信息
Elife. 2022 Dec 20;11:e74320. doi: 10.7554/eLife.74320.
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/m 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/m 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.
背景
儿童时期较高的 BMI 与情绪和行为问题有关,但这些关联可能不是因果关系。先前遗传研究的结果表明存在因果效应,但可能反映了人口统计学和家庭环境的影响。
方法
本研究使用了来自挪威母亲、父亲和儿童队列研究(MoBa)和挪威医学出生登记处(MBRN)的 40949 名 8 岁儿童及其父母的数据。我们调查了 BMI 对 8 岁时抑郁、焦虑和注意缺陷多动障碍(ADHD)症状的影响。我们应用了基于家庭的孟德尔随机化,通过控制父母基因型来解释家族效应。
结果
使用与成人 BMI 相关的遗传变异进行基于家庭的孟德尔随机化估计表明,儿童自身的 BMI 增加了他们的抑郁症状(每增加 5kg/m 的 BMI,beta = 0.26 S.D.,CI = -0.01,0.52,p=0.06)和 ADHD 症状(beta = 0.38 S.D.,CI = 0.09,0.63,p=0.009)。这些估计还表明,母亲 BMI 或相关因素可能独立影响儿童的抑郁症状(母亲 BMI 每增加 5kg/m,beta = 0.11 S.D.,CI:0.02,0.09,p=0.01)。然而,使用与回顾性报告的儿童体型相关的遗传变异进行基于家庭的孟德尔随机化并没有支持 BMI 对这些结果的影响。从任何估计值中几乎没有证据表明父母的 BMI 影响儿童的 ADHD 症状,或者儿童或父母的 BMI 影响儿童的焦虑症状。
结论
我们发现,儿童 BMI 对抑郁和 ADHD 症状的影响证据不一致,对儿童焦虑症状的影响证据很少。父母 BMI 的影响证据有限。在非相关个体样本中进行的遗传研究,或使用与成人 BMI 相关的遗传变异,可能高估了儿童自身 BMI 的因果效应。
资助
本研究由健康基金会资助。它是 HARVEST 合作的一部分,得到了挪威研究理事会的支持。个别合著者的资金来源:欧洲研究理事会、南挪威地区卫生局、挪威研究理事会、诺和诺德基金会、卑尔根大学、南挪威地区卫生局、特隆赫姆莫恩基金会、西挪威地区卫生局、挪威糖尿病协会、英国医学研究理事会。英国医学研究理事会(MRC)和布里斯托大学支持 MRC 综合流行病学单位。