Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity, however, the potential causality between the traits remains unclear. We examined both genetic and prenatal evidence for causality using Mendelian Randomisation (MR) and polygenic risk scores (PRS). We conducted bi-directional MR on ADHD liability and six obesity-related traits using summary statistics from the largest available meta-analyses of genome-wide association studies. We also examined the shared genetic aetiology between ADHD symptoms (inattention and hyperactivity) and body mass index (BMI) by PRS association analysis using longitudinal data from Northern Finland Birth Cohort 1986 (NFBC1986, n = 2984). Lastly, we examined the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms, adjusted for PRS of both traits, in NFBC1986 dataset. Through MR analyses, we found evidence for bidirectional causality between ADHD liability and obesity-related traits. PRS association analyses showed evidence for genetic overlap between ADHD symptoms and BMI. We found no evidence for a difference between inattention and hyperactivity symptoms, suggesting that neither symptom subtype is driving the association. We found evidence for association between maternal pre-pregnancy BMI and offspring ADHD symptoms after adjusting for both BMI and ADHD PRS (association p-value = 0.027 for inattention, p = 0.008 for hyperactivity). These results are consistent with the hypothesis that the co-occurrence between ADHD and obesity has both genetic and prenatal environmental origins.

注意力缺陷/多动障碍（ADHD）通常与肥胖同时发生，然而，这些特征之间的潜在因果关系仍不清楚。我们使用孟德尔随机化 (MR) 和多基因风险评分 (PRS) 检查了遗传和产前因果关系证据。我们使用来自全基因组关联研究的最大可用荟萃分析的汇总统计数据，对 ADHD 倾向和六种肥胖相关特征进行了双向 MR。我们还利用 1986 年北芬兰出生队列 (NFBC1986， n = 2984 ) 的纵向数据，通过 PRS 关联分析检查了 ADHD 症状（注意力不集中和多动）与体重指数 (BMI) 之间的共同遗传病因学 。最后，我们通过对 NFBC1986 数据集中母亲孕前 BMI 和后代 ADHD 症状的关联分析来检查产前环境的影响，并根据这两个特征的 PRS 进行调整。通过 MR 分析，我们发现了 ADHD 倾向与肥胖相关特征之间双向因果关系的证据。PRS 关联分析显示 ADHD 症状与 BMI 之间存在遗传重叠的证据。我们没有发现注意力不集中和多动症状之间存在差异的证据，这表明这两种症状亚型都没有驱动这种关联。在调整 BMI 和 ADHD PRS 后，我们发现了母亲孕前 BMI 与后代 ADHD 症状之间存在关联的证据（注意力不集中的关联p值 = 0.027，多动的关联p  = 0.008）。这些结果与 ADHD 和肥胖同时发生具有遗传和产前环境根源的假设是一致的。