Title | Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Rietveld, CA, Esko, T, Davies, G, Pers, TH, Turley, P, Benyamin, B, Chabris, CF, Emilsson, V, Johnson, AD, Lee, JJ, de Leeuw, C, Marioni, RE, Medland, SE, Miller, MB, Rostapshova, O, van der Lee, SJ, Vinkhuyzen, AAE, Amin, N, Conley, DC, Derringer, J, van Duijn, CM, Fehrmann, R, Franke, LL, Glaeser, EL, Hansell, NK, Hayward, C, Iacono, WG, Ibrahim-Verbaas, CA, Jaddoe, V, Karjalainen, J, Laibson, DI, Lichtenstein, P, Liewald, DC, Magnusson, PKE, Martin, NG, McGue, M, McMahon, G, Pedersen, NL, Pinker, S, Porteous, DJ, Posthuma, D, Rivadeneira, F, Smith, BH, Starr, JM, Tiemeier, H, Timpson, NJ, Trzaskowski, M, Uitterlinden, AG, Verhulst, FC, Ward, ME, Wright, MJ, Smith, GDavey, Deary, IJ, Johannesson, M, Plomin, R, Visscher, PM, Benjamin, DJ, Cesarini, D, Koellinger, PD |
Journal | Proc Natl Acad Sci U S A |
Volume | 111 |
Issue | 38 |
Pagination | 13790-4 |
Date Published | 2014 Sep 23 |
ISSN Number | 1091-6490 |
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 |
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. |
DOI | 10.1073/pnas.1404623111 |
User Guide Notes | |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
Citation Key | 10656 |
PubMed ID | 25201988 |
PubMed Central ID | PMC4183313 |
Grant List | ETM/55 / / Chief Scientist Office / United Kingdom CZB/4/505 / / Chief Scientist Office / United Kingdom R01 AA009367 / AA / NIAAA NIH HHS / United States MC_UU_12013/3 / / Medical Research Council / United Kingdom P30AG012810 / AG / NIA NIH HHS / United States R01 AA011886 / AA / NIAAA NIH HHS / United States R24 HD047879 / HD / NICHD NIH HHS / United States MR/K026992/1 / / Medical Research Council / United Kingdom G0901245 / / Medical Research Council / United Kingdom 102215 / / Wellcome Trust / United Kingdom MC_PC_15018 / / Medical Research Council / United Kingdom R01 DA024417 / DA / NIDA NIH HHS / United States MC_UU_12013/1 / / Medical Research Council / United Kingdom R01 MH066140 / MH / NIMH NIH HHS / United States CZD/16/6/4 / / Chief Scientist Office / United Kingdom MC_PC_U127561128 / / Medical Research Council / United Kingdom T32 MH016880 / MH / NIMH NIH HHS / United States P01AG005842 / AG / NIA NIH HHS / United States G0500079 / / Medical Research Council / United Kingdom T32AG000186-23 / AG / NIA NIH HHS / United States F31 DA029377 / DA / NIDA NIH HHS / United States BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom P01 AG005842 / AG / NIA NIH HHS / United States R37 DA005147 / DA / NIDA NIH HHS / United States P30 AG012810 / AG / NIA NIH HHS / United States T32 AG000186 / AG / NIA NIH HHS / United States P01AG005842-20S2 / AG / NIA NIH HHS / United States G9815508 / / Medical Research Council / United Kingdom R01 DA013240 / DA / NIDA NIH HHS / United States |