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

Magnus Johannesson; Cornelius A. Rietveld; Gail Davies; Tune H. Pers; Patrick Turley; Beben Benyamin; Christopher F. Chabris; Valur Emilsson; Andrew Johnson; James J. Lee; Christiaan de Leeuw C.; Riccardo E. Marioni; Sara E. Medland; Michael Miller; Olga Rostapshova; Anna A E Vinkhuyzen; Najaf Amin; Dalton Conley; Jaime Derringer; Cornerlia 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; N.G. Martin; Matt McGue; George McMahon; Nancy L. Pedersen; Steven Pinker; David J. Porteous; Danielle Posthuma; Fernando Rivadeneira; Blair H. Smith; John M. Starr; Henning Tiemeier; Nicholas J Timpson; André G. Uitterlinden; Frank C. Verhulst; Mary E. Ward; Margaret J. Wright; George Davey-Smith; Ian J. Deary; Robert Plomin; Peter M. Visscher; Daniel J. Benjamin; David Cesarini; Philipp D. Koellinger; Tõnu Esko; Maciej Trzaskowski; Sven J van der Lee

doi:10.1073/pnas.1404623111

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

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

Magnus Johannesson, Cornelius A. Rietveld, Gail Davies, Tune H. Pers, Patrick Turley, Beben Benyamin, Christopher F. Chabris, Valur Emilsson, Andrew Johnson, James J. Lee, …

Proceedings of the National Academy of Sciences, Vol.111(38), pp.13790-13794

2014

DOI: https://doi.org/10.1073/pnas.1404623111

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.

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Title: Common genetic variants associated with cognitive performance identified using the proxy-phenotype method
Creators - without role: Magnus Johannesson - Stockholm School of Economics, Department of Economics
Cornelius A. Rietveld - Erasmus University (NL)
Gail Davies - University of Edinburgh
Tune H. Pers - Boston Children's Hospital
Patrick Turley - Massachusetts General Hospital (US)
Beben Benyamin - University of Queensland (AU)
Christopher F. Chabris - Union College (US)
Valur Emilsson - University of Iceland
Andrew Johnson - National Heart Institute
James J. Lee - University of Minnesota Twin Cities (US)
Christiaan de Leeuw C. - University of Amsterdam (NL)
Riccardo E. Marioni - University of Queensland (AU)
Sara E. Medland - Queensland Institute of Medical Research
Michael Miller - University of Minnesota Twin Cities (US)
Olga Rostapshova - Harvard University (US)
Anna A E Vinkhuyzen - University of Queensland (AU)
Najaf Amin - Erasmus Medical Center
Dalton Conley - Massachusetts Institute of Technology (US)
Jaime Derringer - University of Illinois (US)
Cornerlia M. van Duijn - Leiden University
Rudolf Fehrmann - University of Groningen (NL)
Lude Franke - University of Groningen (NL)
Edward L. Glaeser - Harvard University (US)
Narelle K. Hansell - QIMR Berghofer Medical Research Institute
Caroline Hayward - University of Edinburgh
William G. Iacono - University of Minnesota Twin Cities (US)
Carla Ibrahim-Verbaas - Harvard University (US)
Vincent Jaddoe - Erasmus Medical Center
Juha Karjalainen - University of Groningen (NL)
David Laibson - Harvard University (US)
Paul Lichtenstein - Karolinska Institutet (SE)
David C. Liewald - University of Edinburgh
Patrik K. E. Magnusson - Karolinska Institutet (SE)
N.G. Martin - Queensland Institute of Medical Research
Matt McGue - University of Minnesota Twin Cities (US)
George McMahon - Bristol University (GB)
Nancy L. Pedersen - Karolinska Institutet (SE)
Steven Pinker - University of Cambridge
David J. Porteous - University of Edinburgh
Danielle Posthuma - VU University (NL)
Fernando Rivadeneira - Erasmus University (NL)
Blair H. Smith - University of Dundee
John M. Starr - University of Edinburgh
Henning Tiemeier - Erasmus University (NL)
Nicholas J Timpson - Bristol University (GB)
André G. Uitterlinden - Erasmus University (NL)
Frank C. Verhulst - Erasmus Medical Center
Mary E. Ward - Bristol University (GB)
Margaret J. Wright - QIMR Berghofer Medical Research Institute
George Davey-Smith - Bristol University (GB)
Ian J. Deary - University of Edinburgh
Robert Plomin - King's College London (GB)
Peter M. Visscher - University of Queensland (AU)
Daniel J. Benjamin - Cornell University (US)
David Cesarini - Massachusetts Institute of Technology (US)
Philipp D. Koellinger - Erasmus School of Economics (NL)
Tõnu Esko - University of Tartu
Maciej Trzaskowski - King's College London (GB)
Sven J van der Lee - Erasmus Medical Center
Publication Details: Proceedings of the National Academy of Sciences, Vol.111(38), pp.13790-13794
Publisher: National Academy of Sciences
Number of pages: 5
Identifiers: 991001480698206056
Academic Unit: Department of Economics
Language: English
Resource Type: Journal article

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

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