DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in children

General cognitive ability (g), which is related to many aspects of brain fu nctioning, is one of the most heritable traits in neuroscience. Similarly t o other heritable quantitatively distributed traits, genetic influence on g is likely to be due to the combined action of many genes of small effect [ quantitative trait loci (QTLs)], perhaps several on each chromosome, We use d DNA pooling for the first time to search a chromosome systematically with a dense map of DNA markers for allelic associations with g. We screened 14 7 markers on chromosome 4 such that 85% of the chromosome were estimated to be within 1 cM of a marker. Comparing pooled DNA from 51 children of high g and from 51 controls of average g, 11 significant QTL associations emerge d. The association with three of these 11 markers (D4S2943, MSX1 and D4S160 7) replicated using DNA pooling in independent samples of 50 children of ex tremely high g and 50 controls, Furthermore, all three associations were co nfirmed when each individual was genotyped separately (D4S2943, P = 0.00045 ; MSX1, P = 0.011; D4S1607, P = 0.019). Identifying specific genes responsi ble for such QTL associations will open new windows in cognitive neuroscien ce through which to observe pathways between genes and learning and memory.