Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Biol Psychiatry. 2020 Jun 15;87(12):1052-1062. doi: 10.1016/j.biopsych.2019.11.015. Epub 2019 Nov 29.
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.
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.
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.
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.
注意力缺陷多动障碍（ADHD）是一种神经发育障碍，与受教育程度较低密切相关。最近的一项大型全基因组关联研究确定了与 ADHD 相关的常见基因变异，但大多数遗传结构仍不清楚。
我们使用条件/联合假发现率（FDR）统计框架，对 ADHD（19099 例病例和 34194 例对照）、教育程度（N=842499）和一般智力（N=269867）的独立全基因组关联研究汇总统计数据进行了分析，该框架通过对重叠关联进行条件处理，提高了发现的能力。所鉴定的遗传变异在功能、表达和生物学过程方面进行了特征描述。
我们确定了 58 个独立于连锁不平衡的 ADHD 相关位点（条件 FDR<0.01），其中 30 个与 ADHD 和教育程度或一般智力共享（联合 FDR<0.01），46 个是 ADHD 的新风险位点。
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存在共同遗传基础的假设。尽管所确定的位点的临床实用性仍有待确定，但它们可以用作资源，指导未来旨在解开 ADHD、教育程度和一般智力复杂病因的研究。
