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）是一种神经发育性精神疾病， 严重影响教育和工作表现。然而，目前的研究试图评估 研究ADHD与教育程度的临床和生物学关系 在欧洲高收入国家的样本中。这些研究缺乏多样性， 对不同的个体和情境进行概括。因此，科学界有一种需求， 社区，以更好地调查在异质社会和受影响的少数民族的精神障碍。在 从这个意义上说，社会不平等程度高的国家，如巴西，提供了一个评估的“潜在背景”， 社会和种族认同相关因素对心理健康的影响及其关系 在工作中取得成功。本提案的总体目的是研究生物学（多基因） ADHD、EA和EA相关结果（成绩不及格、大学毕业和功能障碍）之间的联系 文盲）的成年人从对比巴西社会背景。为了实现这一目标，我们提出了一个 一项将联合收割机全基因组和表观基因组数据结合在一起的大样本横断面研究（n = 5，000人）来自巴西两个地区，圣保罗和波尔图阿莱格雷。前沿生物信息学 和统计方法将被应用于整合收集的数据和a）评估，如果欧洲 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。 B）测试它们的影响是否通过对比染色体组和 在巴西人群中观察到的混合物的连续程度;以及c）探索表观遗传标记是否 在这个多样化的人群中，ADHD和EA之间的联系中发挥作用。这项研究旨在揭示 高社会影响表型（ADHD和EA）的潜在病理生理机制。 在基因组学、表观基因组学和基因组学研究中观察到的欧洲中心偏倚可能是非常有害的， 因为它使低收入或中等收入国家的特定人口无法从未来的进步中受益 在基因组学中。文献已经加强了研究异质人群的必要性，例如拉丁美洲人， 建立多种族生物库或生物储存库，其中包含来自不同种族的个体。 环境背景。因此，本研究符合高度相关的科学情景， 所提出的问题是全世界关心的。

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.