Rovira Paula, Demontis Ditte, Sánchez-Mora Cristina, Zayats Tetyana, Klein Marieke, Mota Nina Roth, Weber Heike, Garcia-Martínez Iris, Pagerols Mireia, Vilar-Ribó Laura, Arribas Lorena, Richarte Vanesa, Corrales Montserrat, Fadeuilhe Christian, Bosch Rosa, Martin Gemma Español, Almos Peter, Doyle Alysa E, Grevet Eugenio Horacio, Grimm Oliver, Halmøy Anne, Hoogman Martine, Hutz Mara, Jacob Christian P, Kittel-Schneider Sarah, Knappskog Per M, Lundervold Astri J, Rivero Olga, Rovaris Diego Luiz, Salatino-Oliveira Angelica, da Silva Bruna Santos, Svirin Evgeniy, Sprooten Emma, Strekalova Tatyana, Arias-Vasquez Alejandro, Sonuga-Barke Edmund J S, Asherson Philip, Bau Claiton Henrique Dotto, Buitelaar Jan K, Cormand Bru, Faraone Stephen V, Haavik Jan, Johansson Stefan E, Kuntsi Jonna, Larsson Henrik, Lesch Klaus-Peter, Reif Andreas, Rohde Luis Augusto, Casas Miquel, Børglum Anders D, Franke Barbara, Ramos-Quiroga Josep Antoni, Soler Artigas María, Ribasés Marta
Psychiatric Genetics Unit, Group of Psychiatry, Mental Health, and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.
Neuropsychopharmacology. 2020 Sep;45(10):1617-1626. doi: 10.1038/s41386-020-0664-5. Epub 2020 Apr 12.
Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.
注意缺陷多动障碍(ADHD)是一种常见的神经发育障碍,其特征是存在与年龄不符的注意力不集中、冲动和多动症状,大多数被诊断出的儿童这些症状会持续到成年期。尽管儿童期的多种风险因素可预测ADHD症状持续至成年期,但ADHD随时间变化轨迹背后的遗传结构仍不清楚。我们分别和联合开展针对成人持续性ADHD及儿童ADHD的全基因组关联研究的荟萃分析,并在总共17149例病例和32411例对照的样本中比较他们之间的遗传背景,以研究常见基因变异对ADHD终生风险的贡献。我们的结果显示了9个新的独立基因座,并支持常见基因变异对儿童和成人ADHD的共同贡献。在儿童中未观察到亚组异质性,而该组包括未来缓解型和持续型个体。我们报告了ADHD与其他ADHD相关数据集以及成人、儿童以及两组合并时不同性状和疾病之间相似的遗传相关模式。这些发现证实成人持续性ADHD是一种神经发育障碍,并将ADHD及不同性状背后存在共同遗传结构的现有假设扩展到了终生视角。