Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Int J Epidemiol. 2023 Apr 19;52(2):386-402. doi: 10.1093/ije/dyac128.
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.
注意力缺陷多动障碍（ADHD）是一种由遗传和环境因素共同引起的高度流行的神经发育障碍，通常被认为是负面人生轨迹的起点，包括共病障碍、教育成就低或收入低的风险。在本研究中，我们旨在阐明 ADHD 与广泛相关特征之间的因果关系。
我们使用全基因组关联研究（GWAS）ADHD （n=53293）和 124 种与人体测量、认知功能和智力、早期生活暴露、教育和就业、生活方式和环境、长寿、神经学以及精神健康或人格和心理社会因素相关的特征的汇总统计数据，这些特征可在 MR-Base 数据库中获得（16067≤n≤766345）。为了研究它们与 ADHD 的因果关系，我们使用了双样本 Mendelian 随机化（MR）和一系列敏感性分析，并用使用汇总效应估计的因果分析（CAUSE）验证了 MR 结果，旨在避免潜在的假阳性结果。
我们的研究结果加强了先前 ADHD 易感性与吸烟和重度抑郁症之间存在因果关系的证据，并且与 ADHD 与平均家庭总收入降低（比值比（OR）=0.966，95%可信区间（CrI）=（0.954，0.979））和终生性伴侣数量增加（OR=1.023，95%CrI=（1.013，1.033））的因果关系一致。我们还发现 ADHD 易感性与手臂预测质量和体重（OR=1.452，95%CrI=（1.307，1.614）和 OR=1.430，95%CrI=（1.326，1.539））和看电视时间（OR=1.862，95%CrI=（1.545，2.246））之间存在因果关系，并发现首次性行为年龄的双向影响证据（β=-0.058，95%CrI=（-0.072，-0.044）和 OR=0.413，95%CrI=（0.372，0.457）），完成全日制教育的年龄降低（OR=0.972，95%CrI=（0.962，0.981）和 OR=0.435，95%CrI=（0.356，0.533））和受教育年限（β=-0.036，95%CrI=（-0.048，-0.024）和 OR=0.458，95%CrI=（0.411，0.511））之间存在因果关系。
我们的结果可能有助于解释 ADHD 患者一生中广泛存在的共病特征和共病障碍的部分原因，并为 ADHD 及其负面 ADHD 轨迹的预防策略开辟新的机会。
