AIMS 1) To investigate whether genetic liability to attention-deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS-ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual- or family-related risk factors for SUD could mediate or confound this association. DESIGN Population-based cohort study SETTING AND PARTICIPANTS: ADHD cases in the iPSYCH sample (a Danish case-cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register-based information on hospital diagnoses of SUD was available until December 31, 2016. MEASUREMENTS We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS-ADHD decile to the lowest. FINDINGS PRS-ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11-1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio-economic status) were independently associated with increased risk of SUD. PRS-ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS-ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03-1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales = 1.59, 95% CI: 1.19-2.12, ORmales = 1.18, 95% CI: 0.98-1.42). CONCLUSIONS A higher genetic liability to attention-deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention-deficit/hyperactivity disorder.

中文翻译：

---

ADHD 患者的遗传易感性和物质使用障碍

目的 1) 调查注意力缺陷/多动障碍 (ADHD) 的遗传易感性（由 ADHD 的多基因风险评分 (PRS-ADHD) 索引）是否与 ADHD 患者的物质使用障碍 (SUD) 相关。2) 调查其他与个人或家庭相关的 SUD 风险因素是否可以调节或混淆这种关联。设计基于人群的队列研究 设置和参与者：iPSYCH 样本中的 ADHD 病例（丹麦基因型病例队列样本），1981 年至 2003 年间出生于丹麦（N = 13116）。在 2016 年 12 月 31 日之前，基于登记的 SUD 医院诊断信息可用。 测量 我们估计了任何 SUD 以及不同 SUD 类型（酒精、大麻、和其他非法药物）和严重程度（使用、滥用和成瘾），其影响大小对应于最高 PRS-ADHD 十分位数与最低十分位数的比较。结果 PRS-ADHD 与任何 SUD 相关（OR = 1.30，95% CI：1.11-1.51）。不同类型和严重程度的 SUD 的估计值相似。SUD 的其他风险因素（男性、ADHD 诊断年龄、共病行为问题以及父母因素，包括 SUD、精神障碍和社会经济状况）与 SUD 风险增加独立相关。与其他风险因素相比，PRS-ADHD 解释了 SUD 差异的一小部分（责任量表上的 0.2%）。在调整 SUD 的其他风险因素后，PRS-ADHD 与任何 SUD 之间的关联略有减弱（OR = 1.21，95% CI：1.03-1.41）。此外，女性的关联名义上高于男性（ORfemales = 1.59, 95% CI: 1.19-2.12, ORmales = 1.18, 95% CI: 0.98-1.42）。结论 注意力缺陷/多动障碍的较高遗传易感性似乎与注意力缺陷/多动障碍患者物质使用障碍的较高风险相关。