Testing the association between genetic scores for Attention Deficit Hyperactivity Disorder (ADHD) and health conditions, can help us better understand its complex etiology. Electronic health records linked to genetic data provide an opportunity to test whether genetic scores for ADHD correlate with ADHD and additional health outcomes in a health care context across different age groups. We generated polygenic scores (ADHD-PGS) trained on summary statistics from the latest genome-wide association study of ADHD (N = 55,374) and applied them to genome-wide data from 12,383 unrelated individuals of African-American ancestry and 66,378 unrelated individuals of European ancestry from the Vanderbilt Biobank. Overall, only Tobacco use disorder (TUD) was associated with ADHD-PGS in the African-American ancestry group (Odds ratio [95% confidence intervals] = 1.23[1.16–1.31], p = 9.3 × 10⁻⁰⁹). Eighty-six phenotypes were associated with ADHD-PGS in the European ancestry individuals, including ADHD (OR[95%CIs] = 1.22[1.16–1.29], p = 3.6 × 10⁻¹⁰), and TUD (OR[95%CIs] = 1.22[1.19–1.25], p = 2.8 × 10⁻⁴⁶). We then stratified outcomes by age (ages 0–11, 12–18, 19–25, 26–40, 41–60, and 61–100). Our results suggest that ADHD polygenic scores are associated with ADHD diagnoses early in life and with an increasing number of health conditions throughout the lifespan (even in the absence of ADHD diagnosis). This study reinforces the utility of applying trait-specific PGSs to biobank data, and performing exploratory sensitivity analyses, to probe relationships among clinical conditions.

中文翻译：

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电子健康记录数据中两个遗传血统的注意缺陷多动障碍多基因评分的现象级关联研究

测试注意力缺陷多动障碍 (ADHD) 的遗传评分与健康状况之间的关联，可以帮助我们更好地了解其复杂的病因。与遗传数据相关的电子健康记录提供了一个机会，可以测试 ADHD 的遗传评分是否与 ADHD 以及不同年龄组的医疗保健环境中的其他健康结果相关。我们根据最新的 ADHD 全基因组关联研究的汇总统计数据生成了多基因评分 (ADHD-PGS)（N = 55,374)，并将它们应用于来自范德比尔特生物银行的 12,383 名无关的非裔美国人血统个体和 66,378 名无关的欧洲血统个体的全基因组数据。总体而言，只有烟草使用障碍 (TUD) 与非裔美国人血统组中的 ADHD-PGS 相关（优势比 [95% 置信区间] = 1.23[1.16–1.31]，p = 9.3 × 10  -09 ^）。86 种表型与欧洲血统个体的 ADHD-PGS 相关，包括 ADHD（OR[95%CIs] = 1.22[1.16–1.29]，p = 3.6  × 10 ^-10）和 TUD（OR[95%CIs ] = 1.22[1.19–1.25], p  = 2.8 × 10 ⁻⁴⁶). 然后，我们按年龄（0-11 岁、12-18 岁、19-25 岁、26-40 岁、41-60 岁和 61-100 岁）对结果进行分层。我们的结果表明，ADHD 多基因评分与生命早期的 ADHD 诊断以及整个生命周期中越来越多的健康状况相关（即使没有 ADHD 诊断）。本研究强化了将性状特异性 PGS 应用于生物样本库数据并进行探索性敏感性分析以探究临床条件之间关系的效用。