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

对比环境中教育程度与注意力缺陷/多动症之间的生物学联系

• 批准号: 10526299
• 负责人: DIEGO LUIZ ROVARIS
• 金额: $ 53.95万
• 依托单位: UNIVERSITY OF SAO PAULO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10526299
• 关键词: Accidental Injury; Address; Admixture; Adult; Affect; Age; Area; Attention deficit hyperactivity disorder; Bioinformatics; Biological; Brazil; Characteristics; Childhood; Clinical; Clinical Research; Cognitive; Communities; Complex; Country; Cross-Sectional Studies; DNA Methylation; Data; Disease; Economic Burden; Enrollment; Environment; Epidemiology; Ethnic Origin; European; Failure; Future; Gambling; Genetic; Genomics; Goals; Grant; Health; Heritability; High-Income Populations; Hyperactivity; Impairment; Impulsivity; Income; Individual; Latin America; Life; Life Expectancy; Link; Literature; Mental Health; Mental disorders; Minority; Outcome; Performance; Performance at work; Persons; Phenotype; Play; Population; Population Heterogeneity; Predisposition; Pregnancy in Adolescence; Psyche structure; Public Health; Public Policy; Quality of life; Reporting; Research; Risk; Role; Sampling; Schools; Science; Social Environment; Social Impacts; Socialization; Societies; Substance Use Disorder; Suicide; Symptoms; Testing; Translating; Underachievement; Unemployment; Work; biobank; case control; college; design; epidemiology study; epigenetic marker; epigenome; epigenomics; ethnic disparity; genetic association; genome wide association study; genome-wide; illiteracy; inattention; instrument; interest; methylation biomarker; multi-ethnic; prevent; social; social disparities; social inequality; socioeconomics; success

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.

抽象的 注意缺陷/多动症（ADHD）是一种神经发育的精神病病， 大大损害教育和工作表现。但是，目前寻求评估的研究 多动症与教育程度（EA）之间的临床和生物学关系进行了 在来自高收入国家的欧洲样品中。在这些研究中缺乏多样性阻止了可能性 不同个人和环境的概括。因此，科学中有需求 社区更好地调查异质社会的精神障碍并影响少数民族。在 这种意义上，诸如巴西等社会不平等高的国家提出了评估的“潜在背景” 与社会和种族差异有关的因素（EXPOSOME）对心理健康及其关系的影响 EA和工作中的成功。该建议的一般目的是研究生物学（多基因） ADHD，EA和EA相关结果之间的链接（年级失败，大学完成和功能性 文盲）在与巴西社会背景相比的成年人中。为了实现这一目标，我们建议 横断面研究将在大型样本中结合全基因组和全基因组数据（n =） 5,000）来自两个巴西地区的个人，即圣保罗和Porto Alegre。尖端的生物信息学 并将应用统计方法来整合收集的数据，a）评估欧洲是否是否 ADHD和EA的衍生多基因评分预测靶向表型并复制其生物学 巴西人口的关系； b）测试其效果是否是通过对比的展示体和 在巴西人口中看到的连续混合程度； c）探索是否表观遗传标记 在这个潜水员人群中，在多动症和EA之间的联系中发挥作用。这项研究打算揭示 参与高社会影响表型（ADHD和EA）的潜在病理生理机制。 在基因组，表观基因组学和外展研究中观察到的欧洲中心偏见可能是高度有害的， 由于它阻止了低收入或中等收入国家的特定人群未来的利益 在基因组学中。文献强化了研究异质种群的需求，例如拉丁语 美国，并建立包含来自不同不同个人的多种族生物库或生物库 环境背景。因此，本研究符合高度相关的科学场景，并且 提出的问题是全球兴趣。