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

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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.