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Generalist genes analysis of DNA markers associated with mathematical ability and disability reveals shared influence across ages and abilities.

ABSTRACT: BACKGROUND:The Generalist Genes Hypothesis is based upon quantitative genetic findings which indicate that many of the same genes influence diverse cognitive abilities and disabilities across age. In a recent genome-wide association study of mathematical ability in 10-year-old children, 43 SNP associations were nominated from scans of pooled DNA, 10 of which were validated in an individually genotyped sample. The 4927 children in this genotyped sample have also been studied at 7, 9 and 12 years of age on measures of mathematical ability, as well as on other cognitive and learning abilities. RESULTS:Using these data we have explored the Generalist Genes Hypothesis by assessing the association of the available measures of ability at age 10 and other ages with two composite 'SNP-set' scores, formed from the full set of 43 nominated SNPs and the sub-set of 10 SNPs that were previously found to be associated with mathematical ability at age 10. Both SNP sets yielded significant associations with mathematical ability at ages 7, 9 and 12, as well as with reading and general cognitive ability at age 10. CONCLUSIONS:Although effect sizes are small, our results correspond with those of quantitative genetic research in supporting the Generalist Genes Hypothesis. SNP sets identified on the basis of their associations with mathematical ability at age 10 show associations with mathematical ability at earlier and later ages and show associations of similar magnitude with reading and general cognitive ability. With small effect sizes expected in such complex traits, future studies may be able to capitalise on power by searching for 'generalist genes' using longitudinal and multivariate approaches.

SUBMITTER: Docherty SJ

PROVIDER: S-EPMC2909150 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Generalist genes analysis of DNA markers associated with mathematical ability and disability reveals shared influence across ages and abilities.

Docherty Sophia J SJ Kovas Yulia Y Petrill Stephen A SA Plomin Robert R

BMC genetics 20100705

<h4>Background</h4>The Generalist Genes Hypothesis is based upon quantitative genetic findings which indicate that many of the same genes influence diverse cognitive abilities and disabilities across age. In a recent genome-wide association study of mathematical ability in 10-year-old children, 43 SNP associations were nominated from scans of pooled DNA, 10 of which were validated in an individually genotyped sample. The 4927 children in this genotyped sample have also been studied at 7, 9 and 1 ...[more]

PMID: 20602751

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Project description:Twin research has supported the concept of intelligence (general cognitive ability, g) by showing that genetic correlations between diverse tests of verbal and nonverbal cognitive abilities are greater than 0.50. That is, most of the genes that affect cognitive abilities are highly pleiotropic in the sense that genes that affect one cognitive ability affect all cognitive abilities. The impact of this finding may have been blunted because it depends on the validity of the twin method. Although the assumptions of the twin method have survived indirect tests, it is now possible to test findings from the twin method directly using DNA alone in samples of unrelated individuals, without the assumptions of the twin method. We applied this DNA method, implemented in a software package called Genome-wide Complex Trait Analysis (GCTA), to estimate genetic variance and covariance for two verbal tests and two nonverbal tests using 1.7 million DNA markers genotyped on 2500 unrelated children at age 12; 1900 children also had cognitive data and DNA at age 7. Because each of these individuals is one member of a twin pair, we were able to compare GCTA estimates directly to twin study estimates using the same measures in the same sample. At age 12, GCTA confirmed the results of twin research in showing substantial genetic covariance between verbal and nonverbal composites. The GCTA genetic correlation at age 12 was 1.0 (SE = 0.32), not significantly different from the twin study estimate of 0.60 (SE = 0.09). At age 7, the genetic correlations were 0.31 (SE =0.32) from GCTA and 0.71 (SE = 0.15).from twin analysis. The results from the larger sample and stronger measures at age 12 confirm the twin study results that the genetic architecture of intelligence is driven by pleiotropic effects on diverse cognitive abilities. However, the results at age 7 and the large standard errors of GCTA bivariate genetic correlations suggest the need for further research with larger samples.

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Generalist genes analysis of DNA markers associated with mathematical ability and disability reveals shared influence across ages and abilities.

Publications

Generalist genes analysis of DNA markers associated with mathematical ability and disability reveals shared influence across ages and abilities.

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