"Although there are many types of cognitive ability, they correlate substantially; general cognitive ability (g) indexes this covariance and is an important predictor of many key life outcomes. The PI’s 40-year programme of research has contributed to a once controversial finding that is now widely accepted: Individual differences in g are substantially influenced by genes, as well as the environment. The proposed research will use cutting-edge methodologies to identify genes responsible for the heritability of g.The PI’s research group conducted the first genome-wide association (GWA) studies of g and of specific cognitive abilities using microarrays to genotype common single-nucleotide polymorphisms (SNPs) sampled across the genome. Although GWA studies by the PI and others are beginning to identify a few of the genes responsible for genetic influence on cognitive abilities and disabilities, there remains a problem of ‘missing heritability’, in the search for which the proposed research features two innovations.First, by studying a large sample of individuals with exceptionally high g, statistical power to detect associations of small effect size will be boosted. The project will capitalise on the unique Genetics of High Cognitive Abilities (GHCA) resource recently created by the PI: a sample of 2000 individuals with IQs greater than 160, which represents the 99.997th percentile and exceeds the average IQ of Nobel Prize winners.Second, the project will go beyond reliance on common-SNP microarrays to exploit DNA sequencing, which captures all DNA sequence variation including rare variants. The project will fully sequence the exomes (traditional gene-coding regions) of 1000 of the high-g GHCA individuals and replicate results for targeted DNA variants using the other 1000 high-g individuals. Few discoveries would have greater impact across the social and life sciences – from genes to brain to behaviour – than identifying genes associated with g."