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 注意力缺陷/多动障碍（ADHD）是一种神经发育精神疾病， 然而，目前的研究试图评估。 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，阻止了这种可能性。 因此，科学内部存在需求。 社区更好地调查异质社会和受影响少数群体的精神障碍。 从这个意义上说，社会不平等程度较高的国家，例如巴西，为评估提供了“潜在背景” 社会和种族差异相关因素（暴露组）对心理健康的影响及其关系 与 EA 并在工作中取得成功 该提案的总体目标是研究生物（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 为了实现这一目标，我们提出了一项针对不同巴西社会背景的成年人的研究。 横断面研究，将大样本中的全基因组和表观基因组数据结合起来（n = 5,000）来自巴西两个地区（圣保罗和阿雷格里港）的个人的尖端生物信息学。 统计方法将用于整合收集到的数据，并 a) 评估欧洲是否 ADHD 和 EA 的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暴露组和 巴西人群中观察到的连续混合程度；c) 探索表观遗传标记是否有效 这项研究旨在揭示 ADHD 和 EA 之间的联系。 涉及高社会影响表型（ADHD 和 EA）的潜在病理生理机制。 在基因组、表观基因组和暴露组研究中观察到的欧洲中心偏见可能会令人非常苦恼， 因为它阻止了低收入或中等收入国家的特定人群享受未来进步的好处 基因组学领域的文献强调了研究异质人群的必要性，例如拉丁语人群。 美国的，并建立包含来自不同种族的个体的多种族生物库或生物储存库 因此，本研究符合高度相关的科学场景，并且 所提出的问题引起全世界的关注。