Li Danyang, Choque-Olsson Nora, Jiao Hong, Norgren Nina, Jonsson Ulf, Bölte Sven, Tammimies Kristiina
Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, Stockholm County Council, Stockholm, Sweden.
Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
NPJ Genom Med. 2020 Oct 12;5(1):45. doi: 10.1038/s41525-020-00152-x. eCollection 2020.
Social skills group training (SSGT) is a frequently used behavioral intervention in autism spectrum disorder (ASD), but the effects are moderate and heterogeneous. Here, we analyzed the effect of polygenic risk score (PRS) and common variants in gene sets on the intervention outcome. Participants from the largest randomized clinical trial of SSGT in ASD to date were selected ( = 188, 99 from SSGT, 89 from standard care) to calculate association between the outcomes in the SSGT trial and PRSs for ASD, attention-deficit hyperactivity disorder (ADHD), and educational attainment. In addition, specific gene sets were selected to evaluate their role on intervention outcomes. Among all participants in the trial, higher PRS for ADHD was associated with significant improvement in the outcome measure, the parental-rated Social Responsiveness Scale. The significant association was due to better outcomes in the standard care group for individuals with higher PRS for ADHD (post-intervention: = -4.747, = 0.0129; follow-up: = -5.309, = 0.0083). However, when contrasting the SSGT and standard care group, an inferior outcome in the SSGT group was associated with higher ADHD PRS at follow-up ( = 6.67, = 0.016). Five gene sets within the synaptic category showed a nominal association with reduced response to interventions. We provide preliminary evidence that genetic liability calculated from common variants could influence the intervention outcomes. In the future, larger cohorts should be used to investigate how genetic contribution affects individual response to ASD interventions.
社交技能团体训练（SSGT）是自闭症谱系障碍（ASD）中常用的一种行为干预方法，但其效果中等且存在异质性。在此，我们分析了多基因风险评分（PRS）和基因集中的常见变异对干预结果的影响。我们选取了迄今为止ASD中最大规模的SSGT随机临床试验的参与者（n = 188，99名来自SSGT组，89名来自标准护理组），以计算SSGT试验结果与ASD、注意力缺陷多动障碍（ADHD）和教育程度的PRS之间的关联。此外，还选取了特定的基因集来评估它们在干预结果中的作用。在该试验的所有参与者中，ADHD的较高PRS与结果测量指标（家长评定的社会反应量表）的显著改善相关。这种显著关联是由于ADHD较高PRS的个体在标准护理组中有更好的结果（干预后：β = -4.747，p = 0.0129；随访：β = -5.309，p = 0.0083）。然而，在对比SSGT组和标准护理组时，SSGT组在随访时较差的结果与较高的ADHD PRS相关（β = 6.67，p = 0.016）。突触类别中的五个基因集显示出与干预反应降低存在名义上的关联。我们提供了初步证据，表明从常见变异计算出的遗传易感性可能会影响干预结果。未来，应使用更大的队列来研究遗传因素如何影响个体对ASD干预的反应。
