Our research aims to conduct the largest whole-genome sequencing (WGS)-based genome-wide association study (GWAS) of reaction time to date, examining its genetic overlap with cognitive ability and brain volume. Twin studies indicate moderate heritability (~40-50%) for reaction time, yet few large-scale genomic studies exist, and none have leveraged WGS data to capture rare and structural variants beyond SNP arrays.
Research Questions: What genetic variants influence reaction time performance? How do genetic factors overlap between processing speed, cognitive ability, and brain structure? What biological mechanisms link these traits?
Objectives: (1) Conduct WGS-based GWAS of reaction time, cognitive ability, and brain volume in ~450,000 UK Biobank participants; (2) Estimate heritability contributions from common versus rare variants using GREML; (3) Apply burden and sequence kernel association tests for rare variant analysis; (4) Assess genetic correlations and construct polygenic scores; (5) Perform biological annotation using gene-based analyses, pathway enrichment, and tissue-specific expression data.
Scientific Rationale: Processing speed predicts psychiatric disorders (ADHD, autism, depression, psychosis) and age-related cognitive decline. Understanding genetic architecture could inform early intervention strategies. WGS enables comprehensive variant discovery beyond previous SNP-array limitations, potentially revealing novel biological pathways. By integrating reaction time with brain imaging and cognitive measures, we can identify shared genetic mechanisms underlying information processing speed and broader cognitive function.