Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21694764
TITLE
Educational attainment: a genome wide association study in 9538 Australians.
ABSTRACT
BACKGROUND NlmCategory: 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 NlmCategory: METHODS
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. 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 NlmCategory: RESULTS
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. 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. 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 NlmCategory: CONCLUSIONS
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. 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. 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. 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.
DATE PUBLISHED
2011
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/02/16
accepted 2011/04/13
entrez 2011/06/23 06:00
pubmed 2011/06/23 06:00
medline 2011/11/04 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Martin NW Martin Nicolas W NW Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia. nico.martin@qimr.edu.au
Medland SE Medland Sarah E SE
Verweij KJ Verweij Karin J H KJ
Lee SH Lee S Hong SH
Nyholt DR Nyholt Dale R DR
Madden PA Madden Pamela A PA
Heath AC Heath Andrew C AC
Montgomery GW Montgomery Grant W GW
Wright MJ Wright Margaret J MJ
Martin NG Martin Nicholas G NG
INVESTIGATORS
JOURNAL
VOLUME: 6
ISSUE: 6
TITLE: PloS one
ISOABBREVIATION: PLoS One
YEAR: 2011
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
R01 AA007535 NIAAA NIH HHS United States
R01 AA014041 NIAAA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
R01 MH066206 NIMH NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
R01 AA013326 NIAAA NIH HHS United States
MH66206 NIMH NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
AA14041 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Australia
Cognition physiology
Educational Status physiology
Female physiology
Genome-Wide Association Study physiology
Humans physiology
Linkage Disequilibrium genetics
Male genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's