Project Grant R01MH132965

2/3 AKILI: PHENOTYPIC AND GENETIC CHARACTERIZATION OF ADHD IN KENYA AND SOUTH AFRICA - 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.