小柯机器人

丹麦奥胡斯大学生物医学系Ditte Demontis研究团队报道了儿童期、持续性和晚期诊断的注意力缺陷多动障碍（ADHD）常见和罕见变异的遗传结构差异。相关论文于2022年8月4日发表在《自然—遗传学》杂志上。

他们评估了儿童期 (n = 14,878)、持续性 (n = 1,473) 和晚期诊断 (n = 6,961) ADHD 病例以及 38,303 名对照之间的遗传差异，以及 7,650 名 ADHD 病例和 8,649 名对照中的罕见变异差异。他们确定了四个儿童 ADHD 的全基因组显著位点和一个晚期诊断的 ADHD。他们发现与其他两组相比，持续性 ADHD 患者的多基因评分增加。与晚期诊断的 ADHD 相比，儿童 ADHD 与多动症和自闭症的遗传重叠更高，并且在进化受限的基因中罕见的蛋白质截断变异的负担最高。与儿童 ADHD 相比，晚期诊断的 ADHD 与抑郁症的遗传重叠更大，并且在罕见的蛋白质截短变异中没有增加负担。总体而言，这些结果表明遗传对首次诊断 ADHD 的年龄、ADHD 的持续性和各组之间不同的合并症模式有影响。

据了解，ADHD是一种在儿童期发病的神经发育障碍（儿童多动症），三分之二的受影响个体在成年期继续患有多动症（持续性多动症），有时在成年期被诊断出多动症（晚期诊断多动症）。

附：英文原文

Title: Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder

Author: Rajagopal, Veera M., Duan, Jinjie, Vilar-Rib, Laura, Grove, Jakob, Zayats, Tetyana, Ramos-Quiroga, J. Antoni, Satterstrom, F. Kyle, Artigas, Mara Soler, Bybjerg-Grauholm, Jonas, Bkvad-Hansen, Marie, Als, Thomas D., Rosengren, Anders, Daly, Mark J., Neale, Benjamin M., Nordentoft, Merete, Werge, Thomas, Mors, Ole, Hougaard, David M., Mortensen, Preben B., Ribass, Marta, Brglum, Anders D., Demontis, Ditte

Issue&Volume: 2022-08-04

Abstract: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n=14,878), persistent (n=1,473) and late-diagnosed (n=6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

DOI: 10.1038/s41588-022-01143-7

Source: https://www.nature.com/articles/s41588-022-01143-7

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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