The biological connection between educational attainment and attention-deficit/hyperactivity disorder in contrasting environments

摘要 注意力缺陷/多动障碍(ADHD)是一种神经发育精神疾病， 极大地损害了教育和工作表现。然而，目前寻求评估的研究 研究了ADHD与教育程度(EA)之间的临床和生物学关系 在来自高收入国家的欧洲样本中。这些研究缺乏多样性，这就阻止了这种可能性 针对不同的个人和背景的概括性。因此，在科学内部有一种需求 社区以更好地调查异质社会和受影响的少数群体的精神障碍。在……里面 从这个意义上说，巴西等社会不平等程度较高的国家为评估提供了一个“潜在的背景” 社会和民族差异相关因素对心理健康的影响及其关系 电子艺界和工作上的成功。这项建议的总体目标是研究生物(多基因) ADHD、EA和EA相关结果之间的联系(成绩不及格、大学毕业和功能 文盲)来自不同巴西社会环境的成年人。为了实现这一目标，我们提出了一个 将在大样本中结合全基因组和全表观基因组数据的横断面研究(n= 5,000名来自巴西两个地区--S和阿雷格里港的个人。尖端生物信息学 并将应用统计方法来整合收集的数据，并a)评估欧洲 ADHD和EA的衍生多基因评分可预测目标表型并复制其生物学特性 在巴西人群中的关系；b)测试它们的影响是否受到对比暴露和 在巴西人群中看到的混合的连续程度；以及c)探索表观遗传标记 在这个多样化的人群中，在ADHD和EA之间的联系中发挥作用。这项研究旨在揭示 潜在的病理生理机制与高社会影响表型(ADHD和EA)有关。 在基因组、表观基因组和暴露组学研究中观察到的以欧洲为中心的偏见可能是非常有害的， 因为它阻止了低收入或中等收入国家的特定人口从未来的进步中受益 在基因组学方面。这些文献加强了研究不同种族群体的必要性，比如拉丁语 美国的，并建立包含来自不同种族的个人的多民族生物库或生物库 环境背景。因此，本研究符合一个高度相关的科学假设， 提出的问题引起了全世界的关注。

ABSTRACT Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental psychiatric condition that substantially impairs educational and work performance. However, the current studies seeking to evaluate the clinical and biological relationships between ADHD and educational attainment (EA) were conducted in European samples from high-income countries. The lack of diversity in these studies halts the possibility of generalization for different individuals and contexts. Therefore, there is a demand within the science community to better investigate mental disorders in heterogeneous societies and impacted minorities. In this sense, countries with high social inequalities, such as Brazil, present a "potential context" for assessing the impact of social and ethnic disparity-related factors (exposome) on mental health and its relationship with EA and success at work. The general aim of this proposal is to investigate the biological (polygenic) links between ADHD, EA, and EA-related outcomes (grade failure, college completion, and functional illiteracy) in adult individuals from contrasting Brazilian social contexts. To achieve this, we propose a cross-sectional study that will combine genome-wide and epigenome-wide data in a large sample (n = 5,000) of individuals from two Brazilian regions, São Paulo and Porto Alegre. Cutting-edge bioinformatic and statistical approaches will be applied to integrate the collected data and a) evaluate if the European derived polygenic scores for ADHD and EA predict the targeted phenotypes and replicate their biological relationship in the Brazilian population; b) test if their effects are modulated by contrasting exposomes and the continuous degree of admixture seen in the Brazilian population; and c) explore if epigenetic markers play a role in the links between ADHD and EA in this diverse population. This study intends to reveal potential pathophysiological mechanisms involved in high social impacting phenotypes (ADHD and EA). The Eurocentric bias observed in genomic, epigenomic, and exposomic studies might be highly detrimental, as it prevents specific populations of low- or middle-income countries from the benefits of future advances in genomics. The literature has reinforced the need to study heterogeneous populations, such as Latin America's, and establish multiethnic biobanks or biorepositories containing individuals from different environmental backgrounds. Therefore, the present study fits into a highly relevant scientific scenario, and the raised questions are of worldwide interest.