OBJECTIVE This study investigated outcomes of pharmacogenetic testing of youth with autism spectrum disorder (ASD) referred to a precision medicine clinic and explored associations between patient characteristics and pharmacogenomic testing results. METHODS Records for patients diagnosed with ASD and subsequently referred to a pediatric hospital's precision medicine clinic between July 1, 2010, and June 30, 2020, were reviewed. Pharmacogenetic testing results were abstracted focusing on CYP2D6 and CYP2C19. In addition, we compiled counts of patients' co-occurring diagnoses, histories of adverse drug reactions (ADRs), previously trialed ineffective medications, and previous psychiatric medication changes. Logistic regression models were fit to examine CYP2C19 and CYP2D6 metabolizer status as functions of patient demographics and prereferral medication histories. RESULTS Of 202 patients (mean age = 12.18 yrs), 66% were referred to precision medicine because of poor medication response. Among patients with pharmacogenomic testing results for CYP2D6, 9% were classified as poor metabolizers; among patients with results for CYP2C19, 10% were classified as rapid/ultrarapid metabolizers. Patient demographics and medication response history did not predict pharmacogenomic results. However, the number of co-occurring diagnoses positively predicted the number of nonpsychiatric ADRs and a higher probability of CYP2D6 poor metabolizer status; moreover, nonpsychiatric ADRs positively predicted CYP2C19 rapid/ultrarapid metabolizer status. CONCLUSION In one of the largest reported samples of youth with ASD clinically referred for pharmacogenetic testing, we observed high variability in medication response and yield for actionable results. Our findings suggest potential clinical utility for pharmacogenetic testing and introduce possible clinical profiles associated with metabolizer status.

中文翻译：

---

在精准医学诊所评估自闭症谱系障碍患者的药物遗传学测试。

目的 本研究调查了转诊至精准医学诊所的自闭症谱系障碍 (ASD) 青少年的药物遗传学检测结果，并探讨了患者特征与药物基因组学检测结果之间的关联。方法 对 2010 年 7 月 1 日至 2020 年 6 月 30 日期间被诊断为自闭症谱系障碍 (ASD) 并随后转诊至儿科医院精准医疗诊所的患者的记录进行了审查。药物遗传学检测结果主要集中在 CYP2D6 和 CYP2C19 上。此外，我们还统计了患者同时发生的诊断、药物不良反应 (ADR) 史、之前尝试过的无效药物以及之前的精神科药物变更情况。Logistic 回归模型适合检查 CYP2C19 和 CYP2D6 代谢状态作为患者人口统计数据和转诊前用药史的函数。结果 在 202 名患者（平均年龄 = 12.18 岁）中，66% 由于药物反应不佳而转诊至精准医疗。在具有 CYP2D6 药物基因组学检测结果的患者中，9% 被归类为代谢不良者；在具有 CYP2C19 结果的患者中，10% 被归类为快速/超快速代谢者。患者人口统计数据和药物反应史并不能预测药物基因组结果。然而，同时发生的诊断数量正向预测非精神类 ADR 的数量以及 CYP2D6 代谢状态较差的可能性较高；此外，非精神类 ADR 积极预测 CYP2C19 快速/超快速代谢状态。结论 在临床转诊进行药物遗传学测试的最大报告的 ASD 青少年样本之一中，我们观察到药物反应和可操作结果的产量存在很大差异。我们的研究结果表明药物遗传学测试具有潜在的临床实用性，并介绍了与代谢状态相关的可能的临床特征。