TY - JOUR
T1 - Common genetic variants associated with cognitive performance identified using the proxy-phenotype method
AU - Rietveld, Cornelius A.
AU - Esko, Tõnu
AU - Davies, Gail
AU - Pers, Tune H.
AU - Turley, Patrick
AU - Benyamin, Beben
AU - Chabris, Christopher F.
AU - Emilsson, Valur
AU - Johnson, Andrew D.
AU - Lee, James J.
AU - De Leeuw, Christiaan
AU - Marioni, Riccardo E.
AU - Medland, Sarah E.
AU - Miller, Michael B.
AU - Rostapshova, Olga
AU - Van Der Lee, Sven J.
AU - Vinkhuyzen, Anna A.E.
AU - Amin, Najaf
AU - Conley, Dalton
AU - Derringer, Jaime
AU - Van Duijn, Cornelia M.
AU - Fehrmann, Rudolf
AU - Franke, Lude
AU - Glaeser, Edward L.
AU - Hansell, Narelle K.
AU - Hayward, Caroline
AU - Iacono, William G.
AU - Ibrahim-Verbaas, Carla
AU - Jaddoe, Vincent
AU - Karjalainen, Juha
AU - Laibson, David
AU - Lichtenstein, Paul
AU - Liewald, David C.
AU - Magnusson, Patrik K.E.
AU - Martin, Nicholas G.
AU - McGue, Matt
AU - McMahon, George
AU - Pedersen, Nancy L.
AU - Pinker, Steven
AU - Porteous, David J.
AU - Posthuma, Danielle
AU - Rivadeneira, Fernando
AU - Smithk, Blair H.
AU - Starr, John M.
AU - Tiemeier, Henning
AU - Timpsonm, Nicholas J.
AU - Trzaskowskin, Maciej
AU - Uitterlinden, André G.
AU - Verhulst, Frank C.
AU - Ward, Mary E.
AU - Wright, Margaret J.
AU - Smith, George Davey
AU - Deary, Ian J.
AU - Johannesson, Magnus
AU - Plomin, Robert
AU - Visscher, Peter M.
AU - Benjamin, Daniel J.
AU - Cesarini, David
AU - Koellinger, Philipp D.
PY - 2014/9/23
Y1 - 2014/9/23
N2 - We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype 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.
AB - We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype 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.
UR - https://www.scopus.com/pages/publications/84907285601
U2 - 10.1073/pnas.1404623111
DO - 10.1073/pnas.1404623111
M3 - Article
C2 - 25201988
SN - 0027-8424
VL - 111
SP - 13790
EP - 13794
JO - Proceedings of the National Academy of Sciences of the U.S.A.
JF - Proceedings of the National Academy of Sciences of the U.S.A.
IS - 38
ER -