Background 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. Methods 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. 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]. Conclusions 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.

中文翻译：

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注意缺陷/多动障碍的孟德尔随机化分析：研究广泛的暴露和结果

背景 注意缺陷/多动障碍 (ADHD) 是一种非常普遍的神经发育障碍，由遗传和环境因素共同引起，通常被认为是负面生活轨迹的切入点，包括合并症、教育成绩差或收入低的风险. 在本研究中，我们旨在阐明 ADHD 与一系列相关特征之间的因果关系。方MR-Base 数据库中可用的精神和心理健康或人格和心理社会因素 (16 067 ≤ n ≤ 766 345)。为了研究它们与 ADHD 的因果关系，我们使用了双样本孟德尔随机化 (MR) 和一系列敏感性分析，并使用汇总效应估计 (CAUSE) 的因果分析验证了 MR 结果，旨在避免潜在的假阳性结果。结果 我们的研究结果加强了先前关于 ADHD 易感性对吸烟和重度抑郁症的因果影响的证据，并且与平均家庭总收入下降几率的因果效应一致 [优势比 (OR) = 0.966，95% 可信区间 (CrI) = (0.954, 0.979)] 并增加终生性伴侣数量 [OR = 1.023, 95% CrI = (1.013, 1.033)]。我们还发现了手臂预测质量和重量对 ADHD 的因果影响的证据 [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), 分别] 和花在看电视上的时间 [OR = 1.862, 95% CrI = (1.545, 2.246)]，以及首次性交年龄双向影响的证据 [beta = −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下降几率 [OR = 0.972, 95% CrI = (0.962, 0.981) 和 OR = 0.435, 95% CrI = (0.356, 0.533)，分别] 和受教育年限 [beta = -0.036, 95% CrI = (−0.048, −0.024) 和 OR = 0.458, 95% CrI = (0.411, 0.511)，分别]。结论 我们的研究结果可能有助于解释 ADHD 患者一生中普遍存在的特征和合并症的一部分，并可能为开发 ADHD 和负面 ADHD 轨迹的预防策略开辟新的机会。246)]，以及首次性交年龄双向影响的证据 [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下降的几率 [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 [beta = -0.036 , 95% CrI = (−0.048, −0.024) 和 OR = 0.458, 95% CrI = (0.411, 0.511), 分别]。结论 我们的研究结果可能有助于解释 ADHD 患者一生中普遍存在的特征和合并症的一部分，并可能为开发 ADHD 和负面 ADHD 轨迹的预防策略开辟新的机会。246)]，以及首次性交年龄双向影响的证据 [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下降的几率 [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 [beta = -0.036 , 95% CrI = (−0.048, −0.024) 和 OR = 0.458, 95% CrI = (0.411, 0.511), 分别]。结论 我们的研究结果可能有助于解释 ADHD 患者一生中普遍存在的特征和合并症的一部分，并可能为开发 ADHD 和负面 ADHD 轨迹的预防策略开辟新的机会。413, 95% CrI = (0.372, 0.457), 完成全日制教育年龄下降的几率 [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533) 和受教育年限 [beta = -0.036, 95% CrI = (−0.048, −0.024) 和 OR = 0.458, 95% CrI = (0.411, 0.511)]。结论 我们的研究结果可能有助于解释 ADHD 患者一生中普遍存在的特征和合并症的一部分，并可能为开发 ADHD 和负面 ADHD 轨迹的预防策略开辟新的机会。413, 95% CrI = (0.372, 0.457), 完成全日制教育年龄下降的几率 [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533) 和受教育年限 [beta = -0.036, 95% CrI = (−0.048, −0.024) 和 OR = 0.458, 95% CrI = (0.411, 0.511)]。结论 我们的研究结果可能有助于解释 ADHD 患者一生中普遍存在的特征和合并症的一部分，并可能为开发 ADHD 和负面 ADHD 轨迹的预防策略开辟新的机会。458, 95% CrI = (0.411, 0.511), 分别]。结论 我们的研究结果可能有助于解释 ADHD 患者一生中普遍存在的特征和合并症的一部分，并可能为开发 ADHD 和负面 ADHD 轨迹的预防策略开辟新的机会。458, 95% CrI = (0.411, 0.511), 分别]。结论 我们的研究结果可能有助于解释 ADHD 患者一生中普遍存在的特征和合并症的一部分，并可能为开发 ADHD 和负面 ADHD 轨迹的预防策略开辟新的机会。