@article {10656, title = {Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.}, journal = {Proc Natl Acad Sci U S A}, volume = {111}, year = {2014}, month = {2014 Sep 23}, pages = {13790-4}, 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.

}, keywords = {Cell Adhesion Molecules, Neuronal, Cognition, Female, Humans, Learning, Male, Memory, Multifactorial Inheritance, Nerve Tissue Proteins, Neuronal Plasticity, Octamer Transcription Factors, Polymorphism, Single Nucleotide, Synaptic Transmission}, issn = {1091-6490}, doi = {10.1073/pnas.1404623111}, author = {Cornelius A Rietveld and T{\~o}nu Esko and Gail Davies and Pers, Tune H and Turley, Patrick and Benyamin, Beben and Chabris, Christopher F and Emilsson, Valur and Andrew D Johnson and Lee, James J and Christiaan de Leeuw and Riccardo E Marioni and Sarah E Medland and Michael B Miller and Rostapshova, Olga and Sven J van der Lee and Anna A E Vinkhuyzen and Amin, Najaf and Dalton C Conley and Derringer, Jaime and Cornelia M van Duijn and Fehrmann, Rudolf and Lude L Franke and Edward L Glaeser and Narelle K Hansell and Caroline Hayward and Iacono, William G and Carla A Ibrahim-Verbaas and Vincent Jaddoe and Karjalainen, Juha and David I Laibson and Paul Lichtenstein and David C Liewald and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and McMahon, George and Nancy L Pedersen and Pinker, Steven and David J Porteous and Posthuma, Danielle and Fernando Rivadeneira and Smith, Blair H and John M Starr and Henning Tiemeier and Nicholas J Timpson and Trzaskowski, Maciej and Andr{\'e} G Uitterlinden and Verhulst, Frank C and Mary E Ward and Margaret J Wright and George Davey Smith and Ian J Deary and Johannesson, Magnus and Plomin, Robert and Peter M Visscher and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger} }