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

Cornelius A. Rietveld, Tõnu Esko, Gail Davies, Tune H. Pers, Patrick Turley, Beben Benyamin, Christopher F. Chabris, Valur Emilsson, Andrew D. Johnson, James J. Lee, Christiaan De Leeuw, Riccardo E. Marioni, Sarah E. Medland, Michael B. Miller, Olga Rostapshova, Sven J. Van Der Lee, Anna A.E. Vinkhuyzen, Najaf Amin, Dalton Conley, Jaime DerringerCornelia M. Van Duijn, Rudolf Fehrmann, Lude Franke, Edward L. Glaeser, Narelle K. Hansell, Caroline Hayward, William G. Iacono, Carla Ibrahim-Verbaas, Vincent Jaddoe, Juha Karjalainen, David Laibson, Paul Lichtenstein, David C. Liewald, Patrik K.E. Magnusson, Nicholas G. Martin, Matt McGue, George McMahon, Nancy L. Pedersen, Steven Pinker, David J. Porteous, Danielle Posthuma, Fernando Rivadeneira, Blair H. Smithk, John M. Starr, Henning Tiemeier, Nicholas J. Timpsonm, Maciej Trzaskowskin, André G. Uitterlinden, Frank C. Verhulst, Mary E. Ward, Margaret J. Wright, George Davey Smith, Ian J. Deary, Magnus Johannesson, Robert Plomin, Peter M. Visscher, Daniel J. Benjamin, David Cesarini, Philipp D. Koellinger

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

We 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.

Original languageEnglish (US)
Pages (from-to)13790-13794
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number38
DOIs
StatePublished - Sep 23 2014

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Common genetic variants associated with cognitive performance identified using the proxy-phenotype method'. Together they form a unique fingerprint.

  • Cite this

    Rietveld, C. A., Esko, T., Davies, G., Pers, T. H., Turley, P., Benyamin, B., Chabris, C. F., Emilsson, V., Johnson, A. D., Lee, J. J., De Leeuw, C., Marioni, R. E., Medland, S. E., Miller, M. B., Rostapshova, O., Van Der Lee, S. J., Vinkhuyzen, A. A. E., Amin, N., Conley, D., ... Koellinger, P. D. (2014). Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. Proceedings of the National Academy of Sciences of the United States of America, 111(38), 13790-13794. https://doi.org/10.1073/pnas.1404623111