Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that is known to have a polygenic (i.e., many genes of individually small effects) architecture. Polygenic scores (PGS), which characterize this polygenicity as a single score for a given individual, are considered the state-of-the-art in psychiatric genetics research. Despite the proliferation of ADHD studies adopting this approach and its clinical implications, remarkably little is known about the predictive utility of PGS in ADHD research to date, given that there have not yet been any systematic or meta-analytic reviews of this rapidly developing literature. We meta-analyzed 12 unique effect sizes from ADHD PGS studies, yielding an N = 40,088. These studies, which included a mixture of large population-based cohorts and case–control samples of predominantly European ancestry, yielded a pooled ADHD PGS effect size of r_random = 0.201 (95% CI = [0.144, 0.288]) and an r_fixed = 0.190 (95% CI = [0.180, 0.199]) in predicting ADHD. In other words, ADHD PGS reliably account for between 3.6% (in the fixed effects model) to 4.0% (in the random effects model) of the variance in broadly defined phenotypic ADHD. Findings provide important insights into the genetics of psychiatric outcomes and raise several key questions about the impact of PGS on psychiatric research moving forward. Our review concludes by providing recommendations for future research directions in the use of PGS, including new methods to account for comorbidities, integrating bioinformatics to elucidate biological pathways, and leveraging PGS to test mechanistic models of ADHD.

注意缺陷/多动障碍 (ADHD) 是一种高度遗传的神经发育障碍，已知具有多基因（即，许多基因的单独影响很小）结构。多基因评分 (PGS) 将这种多基因性表征为给定个体的单一评分，被认为是精神病遗传学研究的最新技术。尽管采用这种方法及其临床意义的 ADHD 研究激增，但鉴于尚未对这种快速发展的文献进行任何系统或元分析评论，迄今为止对 PGS 在 ADHD 研究中的预测效用知之甚少。我们对来自 ADHD PGS 研究的 12 个独特的效应量进行了荟萃分析，得出了N = 40,088。这些研究包括大量基于人群的队列和主要欧洲血统的病例对照样本，产生了r _random  = 0.201（95% CI = [0.144, 0.288]）和r_固定的合并 ADHD PGS 效应大小 = 0.190 (95% CI = [0.180, 0.199]) 预测 ADHD。换句话说，ADHD PGS 可靠地解释了广义 ADHD 表型变异的 3.6%（在固定效应模型中）到 4.0%（在随机效应模型中）。研究结果为精神病学结果的遗传学提供了重要的见解，并提出了几个关于 PGS 对精神病学研究向前发展的影响的关键问题。我们的综述最后为 PGS 使用的未来研究方向提供了建议，包括解释合并症的新方法、整合生物信息学以阐明生物学途径，以及利用 PGS 测试 ADHD 的机制模型。