近日，西班牙巴塞罗那大学Natalia Llonga及其团队的最新研究揭示了儿童ADHD症状和诊断的全基因组关联荟萃分析确定了新的基因座和潜在的效应基因。相关论文于2025年9月17日发表于国际顶尖学术期刊《自然—遗传学》杂志上。

研究团队对来自多个评分者、年龄和工具（ADHD_SYMP）的70953个独特个体的290134个注意缺陷/多动障碍（ADHD）症状测量进行了全基因组关联荟萃分析（GWAMA）。接下来，小组将结果与ADHD诊断研究（ADHD_OVERALL）进行meta分析。ADHD_SYMP未返回全基因组显著变异。该团队发现联合ADHD_OVERALL GWAMA鉴定出39个独立位点，其中17个是新的。使用最近开发的基因定位方法，效应基因的精细定位评估模型，研究团队确定了22个潜在的ADHD效应基因，涉及一些新的生物学过程和途径。中度负相关遗传（r_g<-0.40)，存在多种认知特征。在三个队列中，基于ADHDOVERALL的多基因评分（PGSs）优于仅基于ADHD症状和诊断的PGSs。他们的研究结果支持了这样一种观点，即临床ADHD是由ADHD症状所指示的持续责任的极端末端。该课题组人员表明，包括ADHD症状计数有助于识别与ADHD有关的新基因。

附：英文原文

Title: Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes

Author: van der Laan, Camiel M., Ip, Hill F., Schipper, Marijn, Hottenga, Jouke-Jan, St Pourcain, Beate, Zayats, Tetyana, Pool, Ren, Krapohl, Eva M. L., Brikell, Isabell, Soler Artigas, Mara, Cabana-Domnguez, Judit, Nolte, Ilja M., Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Gordon, Scott, Aliev, Fazil, Burt, S. Alexandra, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Vilor-Tejedor, Natlia, Ahluwalia, Tarunveer S., Allegrini, Andrea, Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Bosch, Rosa, Ramos-Quiroga, Josep Antoni, Neumann, Alexander, Ensink, Judith, Grasby, Katrina L., Morosoli, Jos J., Tong, Xiaoran, Marrington, Shelby, Scott, James G., Shabalin, Andrey A., Corley, Robin, Evans, Luke M., Sugden, Karen, Alemany, Silvia, Sass, Lrke, Vinding, Rebecca, Ehli, Erik A., Hagenbeek, Fiona A., Derks, Eske M., Larsson, Henrik, Snieder, Harold, Cecil, Charlotte

Issue&Volume: 2025-09-17

Abstract: We performed a genome-wide association meta-analysis (GWAMA) of 290,134 attention-deficit/hyperactivity disorder (ADHD) symptom measures of 70,953 unique individuals from multiple raters, ages and instruments (ADHDSYMP). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHDOVERALL). ADHDSYMP returned no genome-wide significant variants. We show that the combined ADHDOVERALL GWAMA identified 39 independent loci, of which 17 were new. Using a recently developed gene-mapping method, Fine-mapped Locus Assessment Model of Effector genes, we identified 22 potential ADHD effector genes implicating several new biological processes and pathways. Moderate negative genetic correlations (rg<0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHDOVERALL outperformed PGSs based on ADHD symptoms and diagnosis alone. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts helps to identify new genes implicated in ADHD.

DOI: 10.1038/s41588-025-02295-y

Source: https://www.nature.com/articles/s41588-025-02295-y