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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.

Original publication

DOI

10.1073/pnas.1404623111

Type

Journal article

Journal

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

Publication Date

08/09/2014

Volume

111

Pages

13790 - 13794

Addresses

Department of Applied Economics, Erasmus School of Economics, Erasmus University, 3000 DR, Rotterdam, The Netherlands; Departments of Epidemiology.

Keywords

Humans, Cell Adhesion Molecules, Neuronal, Nerve Tissue Proteins, Cognition, Learning, Memory, Synaptic Transmission, Neuronal Plasticity, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Female, Male, Octamer Transcription Factors