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Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

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dc.contributor.authorRietveld, C.A.
dc.contributor.authorEsko, T.
dc.contributor.authorDavies, G.
dc.contributor.authorPers, T.H.
dc.contributor.authorBenyamin, B.
dc.contributor.authorKoellinger, P.D.
dc.date.issued2014
dc.descriptionData source: Supporting information, http://www.pnas.org/content/suppl/2014/09/06/1404623111.DCSupplemental
dc.description.abstractWe identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2014; 111(38):13790-13794
dc.identifier.doi10.1073/pnas.1404623111
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.orcidBenyamin, B. [0000-0001-5608-2293]
dc.identifier.urihttps://hdl.handle.net/11541.2/130119
dc.language.isoen
dc.publisherNational Academy of Sciences
dc.relation.fundingSocial Science Genetic Association Consortium (SSGAC) SES-1064089
dc.relation.fundingNational Science Foundation
dc.relation.fundingNational Institutes of Health (NIH)/Office of Behavioral and Social Science Research (OBSSR) SES-1064089
dc.relation.fundingRagnar Soderberg Foundation Grant E9/11
dc.relation.fundingSwedish Research Council Grant 412-2013-1061
dc.relation.fundingNational Institute on Aging/NIH Grants P01AG005842
dc.relation.fundingNational Institute on Aging/NIH Grants P01AG005842-20S2
dc.relation.fundingNational Institute on Aging/NIH Grants P30AG012810
dc.relation.fundingNational Institute on Aging/NIH Grants T32AG000186-23
dc.rightsCopyright 2014 PNAS
dc.source.urihttps://doi.org/10.1073/pnas.1404623111
dc.subjectproxy-phenotype method
dc.titleCommon genetic variants associated with cognitive performance identified using the proxy-phenotype method
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916170006001831

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