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

Paul J. Fisher, Dragana Turic, Nigel M. Williams, Peter McGuffin, Philip Asherson, David Ball, Ian Craig, Thalia Eley, Linzy Hill, Karen Chorney, Michael J. Chorney, Camilla P. Benbow, David Lubinski, Robert Plomin, Michael J. Owen

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


General cognitive ability (g), which is related to many aspects of brain functioning, is one of the most heritable traits in neuroscience. Similarly to 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 used 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 147 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 emerged. The association with three of these 11 markers (D4S2943, MSX1 and D4S1607) replicated using DNA pooling in independent samples of 50 children of extremely high g and 50 controls. Furthermore, all three associations were confirmed when each individual was genotyped separately (D4S2943, P = 0.00045; MSX1, P = 0.011; D4S1607, P = 0.019). Identifying specific genes responsible for such QTL associations will open new windows in cognitive neuroscience through which to observe pathways between genes and learning and memory.

Original languageEnglish (US)
Pages (from-to)915-922
Number of pages8
JournalHuman molecular genetics
Issue number5
StatePublished - 1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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