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

ABSTRACT: We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype 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.

SUBMITTER: Rietveld CA

PROVIDER: S-EPMC4183313 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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

Rietveld Cornelius A CA Esko Tõnu T Davies Gail G Pers Tune H TH Turley Patrick P Benyamin Beben B Chabris Christopher F CF Emilsson Valur V Johnson Andrew D AD Lee James J JJ de Leeuw Christiaan C Marioni Riccardo E RE Medland Sarah E SE Miller Michael B MB Rostapshova Olga O van der Lee Sven J SJ Vinkhuyzen Anna A E AA Amin Najaf N Conley Dalton D Derringer Jaime J van Duijn Cornelia M CM Fehrmann Rudolf R Franke Lude L Glaeser Edward L EL Hansell Narelle K NK Hayward Caroline C Iacono William G WG Ibrahim-Verbaas Carla C Jaddoe Vincent V Karjalainen Juha J Laibson David D Lichtenstein Paul P Liewald David C DC Magnusson Patrik K E PK Martin Nicholas G NG McGue Matt M McMahon George G Pedersen Nancy L NL Pinker Steven S Porteous David J DJ Posthuma Danielle D Rivadeneira Fernando F Smith Blair H BH Starr John M JM Tiemeier Henning H Timpson Nicholas J NJ Trzaskowski Maciej M Uitterlinden André G AG Verhulst Frank C FC Ward Mary E ME Wright Margaret J MJ Davey Smith George G Deary Ian J IJ Johannesson Magnus M Plomin Robert R Visscher Peter M PM Benjamin Daniel J DJ Cesarini David D Koellinger Philipp D PD

Proceedings of the National Academy of Sciences of the United States of America 20140908 38

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype 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 si ...[more]

PMID: 25201988

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

Publications

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

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