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

TitleCommon genetic variants associated with cognitive performance identified using the proxy-phenotype method.
Publication TypeJournal Article
Year of Publication2014
AuthorsRietveld, 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
JournalProc Natl Acad Sci U S A
Volume111
Issue38
Pagination13790-4
Date Published2014 Sep 23
ISSN Number1091-6490
KeywordsCell 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.

DOI10.1073/pnas.1404623111
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/25201988?dopt=Abstract

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10656
PubMed ID25201988
PubMed Central IDPMC4183313
Grant ListETM/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