2/3 Akili: Phenotypic and genetic characterization of ADHD in Kenya and South Africa

项目总结 ADHD是一种常见的神经发育障碍，包括注意力困难、冲动和 多动症。这种诊断与教育、职业和健康方面的许多挑战有关 结果，特别是在不治疗的情况下。ADHD的遗传学研究有可能澄清这种疾病的 生物学基础，其异质性，以及它与其他神经精神病学诊断的关系。然而， 对ADHD的遗传学研究在以下方面滞后：(1)样本量，(2)祖先多样性，(3)考虑 表型异质性。Akii旨在解决所有这三个关键差距。阿基里语(斯瓦希里语术语，意为 Mind)将在肯尼亚和南非招收6,000名儿童--4,000名确诊为ADHD的儿童，以及 2000名年龄和血统匹配的对照组。所有参与者将完成详细的行为、认知和 医用表型电池，并提供DNA样本。我们将对所有6000名参与者进行基因特征分析 使用外显子组测序和全基因组基因分型，并公开所有Akii数据和材料 可通过NIMH获得。Akii Data将使Exome提供的ADHD病例数量增加近一倍 测序分析，并在目前的PGC-ADHD Gwas活性基础上增加20%。它将是到目前为止 不同血统数据对这两种分析的最大贡献。Akii将产生一个研究资源， 它具有国际价值，并首次在非洲范围内提供了ADHD的大规模特征。

PROJECT SUMMARY ADHD is a common neurodevelopmental disorder that includes attention difficulty, impulsivity, and hyperactivity. The diagnosis is associated with many challenges to educational, occupational, and health outcomes, particularly when untreated. Genetic studies of ADHD have the potential to clarify the disorder’s biological underpinnings, its heterogeneity, and its relationship to other neuropsychiatric diagnoses. However, genetic research into ADHD lags in terms of: (1) sample size, (2) ancestral diversity, and (3) consideration of phenotypic heterogeneity. Akili is designed to address all three of these critical gaps. Akili (the Swahili term for “mind”) will enroll 6,000 children in Kenya and South Africa – 4,000 with a confirmed diagnosis of ADHD and 2,000 age- and ancestry-matched controls. All participants will complete a detailed behavioral, cognitive, and medical phenotyping battery, and provide a DNA sample. We will genetically characterize all 6,000 participants using exome sequencing and genome-wide genotyping, and make all Akili data and materials publicly available through the NIMH. Akili data will nearly double the number of ADHD cases available for exome sequencing analysis and provide a 20% addition to the current PGC-ADHD GWAS activity. It will be by far the largest contributor of diverse ancestry data to either analysis. Akili will generate a research resource of international value, and provide the first large-scale characterization of ADHD in the African context.