TY - JOUR T1 - Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. JF - Proc Natl Acad Sci U S A Y1 - 2014 A1 - Cornelius A Rietveld A1 - Tõnu Esko A1 - Gail Davies A1 - Pers, Tune H A1 - Turley, Patrick A1 - Benyamin, Beben A1 - Chabris, Christopher F A1 - Emilsson, Valur A1 - Andrew D Johnson A1 - Lee, James J A1 - Christiaan de Leeuw A1 - Riccardo E Marioni A1 - Sarah E Medland A1 - Michael B Miller A1 - Rostapshova, Olga A1 - Sven J van der Lee A1 - Anna A E Vinkhuyzen A1 - Amin, Najaf A1 - Dalton C Conley A1 - Derringer, Jaime A1 - Cornelia M van Duijn A1 - Fehrmann, Rudolf A1 - Lude L Franke A1 - Edward L Glaeser A1 - Narelle K Hansell A1 - Caroline Hayward A1 - Iacono, William G A1 - Carla A Ibrahim-Verbaas A1 - Vincent Jaddoe A1 - Karjalainen, Juha A1 - David I Laibson A1 - Paul Lichtenstein A1 - David C Liewald A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - McMahon, George A1 - Nancy L Pedersen A1 - Pinker, Steven A1 - David J Porteous A1 - Posthuma, Danielle A1 - Fernando Rivadeneira A1 - Smith, Blair H A1 - John M Starr A1 - Henning Tiemeier A1 - Nicholas J Timpson A1 - Trzaskowski, Maciej A1 - André G Uitterlinden A1 - Verhulst, Frank C A1 - Mary E Ward A1 - Margaret J Wright A1 - George Davey Smith A1 - Ian J Deary A1 - Johannesson, Magnus A1 - Plomin, Robert A1 - Peter M Visscher A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger KW - Cell Adhesion Molecules, Neuronal KW - Cognition KW - Female KW - Humans KW - Learning KW - Male KW - Memory KW - Multifactorial Inheritance KW - Nerve Tissue Proteins KW - Neuronal Plasticity KW - Octamer Transcription Factors KW - Polymorphism, Single Nucleotide KW - Synaptic Transmission AB -

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.

VL - 111 IS - 38 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25201988?dopt=Abstract ER -