BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown. METHODS We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment (N = 842,499), and general intelligence (N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes. RESULTS We identified 58 linkage disequilibrium-independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD. CONCLUSIONS These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.

中文翻译：

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鉴定多动症、智力和教育程度之间共享的遗传位点

背景注意力缺陷/多动障碍（ADHD）是一种神经发育障碍，始终与较低的教育程度相关。最近的一项大型全基因组关联研究发现了与多动症相关的常见基因变异，但大多数遗传结构仍然未知。方法 我们使用条件/结合错误发现率 (FDR) 统计框架分析了 ADHD（19,099 例病例和 34,194 例对照）、教育程度（N = 842,499）和一般智力（N = 269,867）的独立全基因组关联研究摘要统计数据通过将 FDR 限制在重叠关联上来增强发现能力。鉴定出的遗传变异在功能、表达和生物过程方面进行了表征。结果我们确定了 58 个与连锁不平衡无关的 ADHD 相关位点（条件 FDR < 0.01），其中 30 个在 ADHD 和教育程度或一般智力之间共享（结合 FDR < 0.01），46 个是 ADHD 的新风险位点。结论 这些结果扩展了先前的遗传和流行病学研究，并支持这些表型之间共享遗传基础的假设。尽管已确定基因座的临床效用仍有待确定，但它们可以用作指导未来研究的资源，旨在理清 ADHD、教育程度和一般智力的复杂病因。