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

C.A. Rietveld, T. Esko, G. Davies, T.H. Pers, P. Turley, B. Benyamin, C.F. Chabris, V. Emilsson, A.D. Johnson, J.J. Lee, C.A. de Leeuw, R.E. Marioni, S.E. Medland, M.B. Miller, O. Rostapshova, S.J. van der Lee, A.A. Vinkhuyzen, N. Amin, D. Conley, J. Derringer & 39 others C.M. van Duijn, R. Fehrmann, L. Franke, E.L. Glaeser, N.K. Hansell, C. Hayward, W.G. Lacono, C.A. Ibrahim-Verbaas, V. Jaddoe, J. Karjalainen, D. Laibson, P. Lichtenstein, D.C. Liewald, P.K. Magnusson, N.G. Martin, M. McGue, G. McMahon, N.L. Pedersen, S. Pinker, D.J. Porteous, D. Posthuma, F. Rivadeneira, B.H. Smith, J. M. Starr, H. Tiemeier, N.J. Timpson, M. Trzaskowski, A. G. Uitterlinden, F.C. Verhulst, M.E. Ward, M.J. Wright, G. Davey Smith, I. J. Deary, M. Johannesson, R. Plomin, P. M. Visscher, D.J. Benjamin, D. Cesarini, P.D. Koellinger

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)13790-13794
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number38
DOIs
Publication statusPublished - 2014

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Proxy
Single Nucleotide Polymorphism
Phenotype
Education
Neuronal Plasticity
Genome-Wide Association Study
Computational Biology
Genes
Neurotransmitter Agents
Dementia
Learning

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Rietveld, C.A. ; Esko, T. ; Davies, G. ; Pers, T.H. ; Turley, P. ; Benyamin, B. ; Chabris, C.F. ; Emilsson, V. ; Johnson, A.D. ; Lee, J.J. ; de Leeuw, C.A. ; Marioni, R.E. ; Medland, S.E. ; Miller, M.B. ; Rostapshova, O. ; van der Lee, S.J. ; Vinkhuyzen, A.A. ; Amin, N. ; Conley, D. ; Derringer, J. ; van Duijn, C.M. ; Fehrmann, R. ; Franke, L. ; Glaeser, E.L. ; Hansell, N.K. ; Hayward, C. ; Lacono, W.G. ; Ibrahim-Verbaas, C.A. ; Jaddoe, V. ; Karjalainen, J. ; Laibson, D. ; Lichtenstein, P. ; Liewald, D.C. ; Magnusson, P.K. ; Martin, N.G. ; McGue, M. ; McMahon, G. ; Pedersen, N.L. ; Pinker, S. ; Porteous, D.J. ; Posthuma, D. ; Rivadeneira, F. ; Smith, B.H. ; Starr, J. M. ; Tiemeier, H. ; Timpson, N.J. ; Trzaskowski, M. ; Uitterlinden, A. G. ; Verhulst, F.C. ; Ward, M.E. ; Wright, M.J. ; Davey Smith, G. ; Deary, I. J. ; Johannesson, M. ; Plomin, R. ; Visscher, P. M. ; Benjamin, D.J. ; Cesarini, D. ; Koellinger, P.D. / Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 38. pp. 13790-13794.
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abstract = "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.",
author = "C.A. Rietveld and T. Esko and G. Davies and T.H. Pers and P. Turley and B. Benyamin and C.F. Chabris and V. Emilsson and A.D. Johnson and J.J. Lee and {de Leeuw}, C.A. and R.E. Marioni and S.E. Medland and M.B. Miller and O. Rostapshova and {van der Lee}, S.J. and A.A. Vinkhuyzen and N. Amin and D. Conley and J. Derringer and {van Duijn}, C.M. and R. Fehrmann and L. Franke and E.L. Glaeser and N.K. Hansell and C. Hayward and W.G. Lacono and C.A. Ibrahim-Verbaas and V. Jaddoe and J. Karjalainen and D. Laibson and P. Lichtenstein and D.C. Liewald and P.K. Magnusson and N.G. Martin and M. McGue and G. McMahon and N.L. Pedersen and S. Pinker and D.J. Porteous and D. Posthuma and F. Rivadeneira and B.H. Smith and Starr, {J. M.} and H. Tiemeier and N.J. Timpson and M. Trzaskowski and Uitterlinden, {A. G.} and F.C. Verhulst and M.E. Ward and M.J. Wright and {Davey Smith}, G. and Deary, {I. J.} and M. Johannesson and R. Plomin and Visscher, {P. M.} and D.J. Benjamin and D. Cesarini and P.D. Koellinger",
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Rietveld, CA, Esko, T, Davies, G, Pers, TH, Turley, P, Benyamin, B, Chabris, CF, Emilsson, V, Johnson, AD, Lee, JJ, de Leeuw, CA, Marioni, RE, Medland, SE, Miller, MB, Rostapshova, O, van der Lee, SJ, Vinkhuyzen, AA, Amin, N, Conley, D, Derringer, J, van Duijn, CM, Fehrmann, R, Franke, L, Glaeser, EL, Hansell, NK, Hayward, C, Lacono, WG, Ibrahim-Verbaas, CA, Jaddoe, V, Karjalainen, J, Laibson, D, Lichtenstein, P, Liewald, DC, Magnusson, PK, 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, Davey Smith, G, Deary, IJ, Johannesson, M, Plomin, R, Visscher, PM, Benjamin, DJ, Cesarini, D & Koellinger, PD 2014, 'Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.' Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 38, pp. 13790-13794. https://doi.org/10.1073/pnas.1404623111

Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. / Rietveld, C.A.; Esko, T.; Davies, G.; Pers, T.H.; Turley, P.; Benyamin, B.; Chabris, C.F.; Emilsson, V.; Johnson, A.D.; Lee, J.J.; de Leeuw, C.A.; Marioni, R.E.; Medland, S.E.; Miller, M.B.; Rostapshova, O.; van der Lee, S.J.; Vinkhuyzen, A.A.; Amin, N.; Conley, D.; Derringer, J.; van Duijn, C.M.; Fehrmann, R.; Franke, L.; Glaeser, E.L.; Hansell, N.K.; Hayward, C.; Lacono, W.G.; Ibrahim-Verbaas, C.A.; Jaddoe, V.; Karjalainen, J.; Laibson, D.; Lichtenstein, P.; Liewald, D.C.; Magnusson, P.K.; Martin, N.G.; McGue, M.; McMahon, G.; Pedersen, N.L.; Pinker, S.; Porteous, D.J.; Posthuma, D.; Rivadeneira, F.; Smith, B.H.; Starr, J. M.; Tiemeier, H.; Timpson, N.J.; Trzaskowski, M.; Uitterlinden, A. G.; Verhulst, F.C.; Ward, M.E.; Wright, M.J.; Davey Smith, G.; Deary, I. J.; Johannesson, M.; Plomin, R.; Visscher, P. M.; Benjamin, D.J.; Cesarini, D.; Koellinger, P.D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 38, 2014, p. 13790-13794.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.

AU - Rietveld, C.A.

AU - Esko, T.

AU - Davies, G.

AU - Pers, T.H.

AU - Turley, P.

AU - Benyamin, B.

AU - Chabris, C.F.

AU - Emilsson, V.

AU - Johnson, A.D.

AU - Lee, J.J.

AU - de Leeuw, C.A.

AU - Marioni, R.E.

AU - Medland, S.E.

AU - Miller, M.B.

AU - Rostapshova, O.

AU - van der Lee, S.J.

AU - Vinkhuyzen, A.A.

AU - Amin, N.

AU - Conley, D.

AU - Derringer, J.

AU - van Duijn, C.M.

AU - Fehrmann, R.

AU - Franke, L.

AU - Glaeser, E.L.

AU - Hansell, N.K.

AU - Hayward, C.

AU - Lacono, W.G.

AU - Ibrahim-Verbaas, C.A.

AU - Jaddoe, V.

AU - Karjalainen, J.

AU - Laibson, D.

AU - Lichtenstein, P.

AU - Liewald, D.C.

AU - Magnusson, P.K.

AU - Martin, N.G.

AU - McGue, M.

AU - McMahon, G.

AU - Pedersen, N.L.

AU - Pinker, S.

AU - Porteous, D.J.

AU - Posthuma, D.

AU - Rivadeneira, F.

AU - Smith, B.H.

AU - Starr, J. M.

AU - Tiemeier, H.

AU - Timpson, N.J.

AU - Trzaskowski, M.

AU - Uitterlinden, A. G.

AU - Verhulst, F.C.

AU - Ward, M.E.

AU - Wright, M.J.

AU - Davey Smith, G.

AU - Deary, I. J.

AU - Johannesson, M.

AU - Plomin, R.

AU - Visscher, P. M.

AU - Benjamin, D.J.

AU - Cesarini, D.

AU - Koellinger, P.D.

PY - 2014

Y1 - 2014

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.

U2 - 10.1073/pnas.1404623111

DO - 10.1073/pnas.1404623111

M3 - Article

VL - 111

SP - 13790

EP - 13794

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

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

SN - 0027-8424

IS - 38

ER -