Core Viewpoint - The article discusses a significant study identifying rare genetic variants associated with Attention Deficit Hyperactivity Disorder (ADHD), revealing that individuals carrying these variants have a substantially higher risk of developing ADHD compared to the general population [4][9]. Group 1: ADHD Overview - ADHD is a neurodevelopmental disorder affecting approximately 5% of children globally, with about half of these cases persisting into adulthood, leading to various severe consequences [3]. - The study highlights the importance of understanding the biological mechanisms driving ADHD for future treatment and intervention strategies [3]. Group 2: Research Findings - A groundbreaking study published in Nature identified three rare genetic variants—MAP1A, ANO8, and ANK2—significantly linked to ADHD risk, with individuals carrying these variants having a 5.55 to 15.31 times higher risk of developing the disorder [4][9]. - The research involved a large sample size of 8,895 ADHD patients and 53,780 healthy controls, focusing on rare coding gene variants that can severely impact protein function [7]. Group 3: Genetic Mechanisms - MAP1A is crucial for microtubule assembly and neuronal structure, while ANO8 and ANK2 are involved in calcium ion transport, indicating that ion channel dysfunction plays a significant role in ADHD [11]. - The study found that these rare variants not only increase the risk of ADHD but also significantly affect cognitive function and socioeconomic status, with carriers being 24% more likely to complete only basic education and 28% more likely to experience low socioeconomic status [14]. Group 4: Combined Genetic Effects - The research explored the combined effects of common and rare genetic variants, revealing that they contribute to ADHD risk additively, with rare variants acting as risk accelerators [17]. Group 5: Implications for Future Research - The findings suggest that the identified genes explain only 5.2% of the heritability associated with rare variants, indicating that more ADHD risk genes remain to be discovered [19]. - Long-term implications include the potential for developing precise diagnostic methods, personalized treatment strategies, and reducing stigma associated with ADHD by clarifying its biological basis [20].