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Educational attainment: a genome wide association study in 9538 Australians.

Martin NW, Medland SE, Verweij KJ, Lee SH, Nyholt DR, Madden PA, Heath AC, Montgomery GW, Wright MJ, Martin NG - PLoS ONE (2011)

Bottom Line: The best SNP fell short of having a genome-wide significant p-value (p = 9.77×10(-7)).The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample.While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia. nico.martin@qimr.edu.au

ABSTRACT

Background: Correlations between Educational Attainment (EA) and measures of cognitive performance are as high as 0.8. This makes EA an attractive alternative phenotype for studies wishing to map genes affecting cognition due to the ease of collecting EA data compared to other cognitive phenotypes such as IQ.

Methodology: In an Australian family sample of 9538 individuals we performed a genome-wide association scan (GWAS) using the imputed genotypes of ∼2.4 million single nucleotide polymorphisms (SNP) for a 6-point scale measure of EA. Top hits were checked for replication in an independent sample of 968 individuals. A gene-based test of association was then applied to the GWAS results. Additionally we performed prediction analyses using the GWAS results from our discovery sample to assess the percentage of EA and full scale IQ variance explained by the predicted scores.

Results: The best SNP fell short of having a genome-wide significant p-value (p = 9.77×10(-7)). In our independent replication sample six SNPs among the top 50 hits pruned for linkage disequilibrium (r(2)<0.8) had a p-value<0.05 but only one of these SNPs survived correction for multiple testing--rs7106258 (p = 9.7*10(-4)) located in an intergenic region of chromosome 11q14.1. The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample.

Conclusion: While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted. Overall, the absence of genome-wide significant p-values in our large discovery sample confirmed the high polygenic architecture of EA. Only the assembly of large samples or meta-analytic efforts will be able to assess the implication of common DNA polymorphisms in the etiology of EA.

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Related in: MedlinePlus

Transformation applied to the original education scales (1 to 3) to obtain a new harmonized scale across studies.
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pone-0020128-g001: Transformation applied to the original education scales (1 to 3) to obtain a new harmonized scale across studies.

Mentions: Self reported educational attainment (EA) was collected as part as of questionnaires and telephone interviews. In the adult cohorts (1 and 2) three similar education scales were used to collect EA depending on the study in which an individual participated (fig. 1). Each individual score was transformed to create a new 6-level EA scale harmonised across the studies, with 1 = 7 years or less of schooling, 2 = 8 to 10 years of schooling, 3 = 8 to 10 years of schooling + apprenticeship or 11 to 12 years of schooling or 12 years of schooling + apprenticeship, 4 = teacher college or technical college, 5 = university undergraduate training and 6 = university postgraduate training (fig. 1). For a number of individuals (n = 5314) multiple reports of EA were available and the highest education level reported was selected for analysis. In cohort 3, EA was also assessed as part of a questionnaire that the parents of the adolescent twins answered while their children underwent cognitive testing. EA was recorded with one of the scales previously used in the adult cohorts (Figure 1). All individuals that were included in the GWAS analysis were at least 21 years of age (the standard age of first degree graduation). Descriptive statistics of the age and educational attainment of the participants according to their study of origin can be found in Table S1.


Educational attainment: a genome wide association study in 9538 Australians.

Martin NW, Medland SE, Verweij KJ, Lee SH, Nyholt DR, Madden PA, Heath AC, Montgomery GW, Wright MJ, Martin NG - PLoS ONE (2011)

Transformation applied to the original education scales (1 to 3) to obtain a new harmonized scale across studies.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111411&req=5

pone-0020128-g001: Transformation applied to the original education scales (1 to 3) to obtain a new harmonized scale across studies.
Mentions: Self reported educational attainment (EA) was collected as part as of questionnaires and telephone interviews. In the adult cohorts (1 and 2) three similar education scales were used to collect EA depending on the study in which an individual participated (fig. 1). Each individual score was transformed to create a new 6-level EA scale harmonised across the studies, with 1 = 7 years or less of schooling, 2 = 8 to 10 years of schooling, 3 = 8 to 10 years of schooling + apprenticeship or 11 to 12 years of schooling or 12 years of schooling + apprenticeship, 4 = teacher college or technical college, 5 = university undergraduate training and 6 = university postgraduate training (fig. 1). For a number of individuals (n = 5314) multiple reports of EA were available and the highest education level reported was selected for analysis. In cohort 3, EA was also assessed as part of a questionnaire that the parents of the adolescent twins answered while their children underwent cognitive testing. EA was recorded with one of the scales previously used in the adult cohorts (Figure 1). All individuals that were included in the GWAS analysis were at least 21 years of age (the standard age of first degree graduation). Descriptive statistics of the age and educational attainment of the participants according to their study of origin can be found in Table S1.

Bottom Line: The best SNP fell short of having a genome-wide significant p-value (p = 9.77×10(-7)).The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample.While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia. nico.martin@qimr.edu.au

ABSTRACT

Background: Correlations between Educational Attainment (EA) and measures of cognitive performance are as high as 0.8. This makes EA an attractive alternative phenotype for studies wishing to map genes affecting cognition due to the ease of collecting EA data compared to other cognitive phenotypes such as IQ.

Methodology: In an Australian family sample of 9538 individuals we performed a genome-wide association scan (GWAS) using the imputed genotypes of ∼2.4 million single nucleotide polymorphisms (SNP) for a 6-point scale measure of EA. Top hits were checked for replication in an independent sample of 968 individuals. A gene-based test of association was then applied to the GWAS results. Additionally we performed prediction analyses using the GWAS results from our discovery sample to assess the percentage of EA and full scale IQ variance explained by the predicted scores.

Results: The best SNP fell short of having a genome-wide significant p-value (p = 9.77×10(-7)). In our independent replication sample six SNPs among the top 50 hits pruned for linkage disequilibrium (r(2)<0.8) had a p-value<0.05 but only one of these SNPs survived correction for multiple testing--rs7106258 (p = 9.7*10(-4)) located in an intergenic region of chromosome 11q14.1. The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample.

Conclusion: While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted. Overall, the absence of genome-wide significant p-values in our large discovery sample confirmed the high polygenic architecture of EA. Only the assembly of large samples or meta-analytic efforts will be able to assess the implication of common DNA polymorphisms in the etiology of EA.

Show MeSH
Related in: MedlinePlus