title: Educational attainment: a genome wide association study in 9538 Australians.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia. nico.martin@qimr.edu.au
authors.forename: Nicolas W
authors.initials: NW
authors.lastname: Martin
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.forename: Karin J H
authors.initials: KJ
authors.lastname: Verweij
authors.forename: S Hong
authors.initials: SH
authors.lastname: Lee
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Madden
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
mesh_terms: D000328:Adult; D001315:Australia; D003071:Cognition / Q000502:physiology; D004522:Educational Status; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics