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

项目摘要 ADHD是一种常见的神经发育障碍，包括注意力困难，冲动， 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，特别是在未经治疗的情况下。ADHD的遗传学研究有可能阐明这种疾病的 生物学基础、异质性及其与其他神经精神病诊断的关系。然而，在这方面， 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Akili旨在解决所有这三个关键差距。Akili（斯瓦希里语， “mind”）将在肯尼亚和南非招募6,000名儿童，其中4,000名被确诊患有多动症， 2,000名年龄和血统匹配的对照组。所有参与者将完成一个详细的行为，认知， 医学表型分析电池，并提供DNA样本。我们将对所有6,000名参与者进行基因分析 使用外显子组测序和全基因组基因分型，并公开所有Akili数据和材料 通过NIMH。Akili数据将使外显子组可用的ADHD病例数量增加近一倍 测序分析，并提供了20%的增加，目前PGC-ADHD GWAS活性。这将是迄今为止 最大的贡献者不同的祖先数据的分析。Akili将产生一个研究资源， 国际价值，并提供了在非洲背景下ADHD的第一个大规模表征。

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.