Search

Your search keyword '"Chiba-Falek, O."' showing total 11 results
Start Over Author "Chiba-Falek, O." Database OpenAIRE
11 results on '"Chiba-Falek, O."'

1. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Author

Lam, M. Chen, C.-Y. Ge, T. Xia, Y. Hill, D.W. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Stahl, E.A. Huckins, L. Liewald, D.C. Djurovic, S. Melle, I. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Hartmann, A.M. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Koltai, D.C. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Smyrnis, N. Bilder, R.M. Freimer, N.B. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Huang, H. Liu, C. Malhotra, A.K. Lencz, T.

Abstract

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing. © 2021, The Author(s).

Published
2021

2. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., Lee, S.J. van der, Ware, E.B., Windham, B.G., Wright, M.J., Yang, J.Y., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Bohmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kahonen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Hellard, S. le, Lee, T., Lehtimaki, T., Li, S.C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikainen, L.P., Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumare, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., Jager, P.L. de, Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hagg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Raikkonen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., Duijn, C.M. van, Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Published
2019

3. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S. E., TRAMPUSH, J. W., LUCIANO, M., HILL, W. D., HAGENAARS, S. P., RITCHIE, S. J., MARIONI, R. E., FAWNS-RITCHIE, C., LIEWALD, D. C. M., OKELY, J. A., AHOLA-OLLI, A. V., BARNES, C. L. K., Bertram, L., BIS, J. C., BURDICK, K. E., CHRISTOFOROU, A., DEROSSE, P., Djurovic, S., ESPESETH, T., GIAKOUMAKI, S., GIDDALURU, S., GUSTAVSON, D. E., Hayward, C., Hofer, E., KARLSSON, R., KNOWLES, E., Lahti, J., Leber, M., MATHER, K. A., Melle, I., Morris, D., OLDMEADOW, C., PALVIAINEN, T., PAYTON, A., PAZOKI, R., PETROVIC, K., Reynolds, C. A., SARGURUPREMRAJ, M., Scholz, M., Smith, J. A., SMITH, A. V., TERZIKHAN, N., THALAMUTHU, A., TROMPET, S., VAN DER LEE, S. J., WARE, E. B., WINDHAM, B. G., WRIGHT, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., ANDREASSEN, O. A., ARMSTRONG, N. J., ASSAREH, A. A., ATTIA, J. R., ATTIX, D., AVRAMOPOULOS, D., BENNETT, D. A., BOHMER, A. C., BOYLE, P. A., BRODATY, H., Campbell, H., CANNON, T. D., CIRULLI, E. T., CONGDON, E., CONLEY, E. D., CORLEY, J., COX, S. R., DALE, A. M., DEHGHAN, A., Dick, D., Dickinson, D., ERIKSSON, J. G., EVANGELOU, E., FAUL, J. D., Ford, I., FREIMER, N. A., Gao, H., Giegling, I., GILLESPIE, N. A., GORDON, S. D., GOTTESMAN, R. F., GRISWOLD, M. E., GUDNASON, V., HARRIS, T. B., HARTMANN, A. M., Hatzimanolis, A., Heiss, G., HOLLIDAY, E. G., Joshi, P. K., KAHONEN, M., KARDIA, S. L. R., KARLSSON, I., KLEINEIDAM, L., KNOPMAN, D. S., KOCHAN, N. A., Konte, B., KWOK, J. B., LE HELLARD, S., Lee, T., LEHTIMAKI, T., Li, S. C., Lill, C. M., Liu, T., KOINI, M., London, E., LONGSTRETH, W. T., Jr., LOPEZ, O. L., LOUKOLA, A., LUCK, T., LUNDERVOLD, A. J., LUNDQUIST, A., LYYTIKAINEN, L. P., Martin, N. G., MONTGOMERY, G. W., MURRAY, A. D., NEED, A. C., NOORDAM, R., Nyberg, L., OLLIER, W., PAPENBERG, G., PATTIE, A., POLASEK, O., POLDRACK, R. A., PSATY, B. M., REPPERMUND, S., RIEDEL-HELLER, S. G., ROSE, R. J., ROTTER, J. I., ROUSSOS, P., ROVIO, S. P., SABA, Y., SABB, F. W., SACHDEV, P. S., SATIZABAL, C. L., Schmid, M., Scott, R. J., SCULT, M. A., SIMINO, J., SLAGBOOM, P. E., SMYRNIS, N., Soumare, A., Stefanis, N. C., STOTT, D. J., STRAUB, R. E., SUNDET, K., Taylor, A. M., TAYLOR, K. D., TZOULAKI, I., Tzourio, C., Uitterlinden, A., Vitart, V., VOINESKOS, A. N., Kaprio, J., Wagner, M., Wagner, H., WEINHOLD, L., WEN, K. H., WIDEN, E., Yang, Q., Zhao, W., ADAMS, H. H. H., ARKING, D. E., Bilder, R. M., BITSIOS, P., BOERWINKLE, E., CHIBA-FALEK, O., Corvin, A., DE JAGER, P. L., Debette, S., Donohoe, G., Elliott, P., FITZPATRICK, A. L., Gill, M., GLAHN, D. C., HAGG, S., HANSELL, N. K., HARIRI, A. R., Ikram, M. A., JUKEMA, J. W., VUOKSIMAA, E., KELLER, M. C., KREMEN, W. S., LAUNER, L., LINDENBERGER, U., Palotie, A., PEDERSEN, N. L., PENDLETON, N., PORTEOUS, D. J., RAIKKONEN, K., RAITAKARI, O. T., Ramirez, A., REINVANG, I., RUDAN, I., DAN, Rujescu, Schmidt, R., Schmidt, H., SCHOFIELD, P. W., STARR, J. M., STEEN, V. M., TROLLOR, J. N., TURNER, S. T., VAN DUIJN, C. M., VILLRINGER, A., WEINBERGER, D. R., WEIR, D. R., WILSON, J. F., Malhotra, A., MCINTOSH, A. M., GALE, C. R., SESHADRI, S., MOSLEY, T. H., Jr., BRESSLER, J., Lencz, T., DEARY, I. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
VINTAGE, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTHY, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Published
2019

4. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x)

Author

Davies, G. Lam, M. Harris, S.E. Trampush, J.W. Luciano, M. Hill, W.D. Hagenaars, S.P. Ritchie, S.J. Marioni, R.E. Fawns-Ritchie, C. Liewald, D.C.M. Okely, J.A. Ahola-Olli, A.V. Barnes, C.L.K. Bertram, L. Bis, J.C. Burdick, K.E. Christoforou, A. DeRosse, P. Djurovic, S. Espeseth, T. Giakoumaki, S. Giddaluru, S. Gustavson, D.E. Hayward, C. Hofer, E. Ikram, M.A. Karlsson, R. Knowles, E. Lahti, J. Leber, M. Li, S. Mather, K.A. Melle, I. Morris, D. Oldmeadow, C. Palviainen, T. Payton, A. Pazoki, R. Petrovic, K. Reynolds, C.A. Sargurupremraj, M. Scholz, M. Smith, J.A. Smith, A.V. Terzikhan, N. Thalamuthu, A. Trompet, S. van der Lee, S.J. Ware, E.B. Windham, B.G. Wright, M.J. Yang, J. Yu, J. Ames, D. Amin, N. Amouyel, P. Andreassen, O.A. Armstrong, N.J. Assareh, A.A. Attia, J.R. Attix, D. Avramopoulos, D. Bennett, D.A. Böhmer, A.C. Boyle, P.A. Brodaty, H. Campbell, H. Cannon, T.D. Cirulli, E.T. Congdon, E. Conley, E.D. Corley, J. Cox, S.R. Dale, A.M. Dehghan, A. Dick, D. Dickinson, D. Eriksson, J.G. Evangelou, E. Faul, J.D. Ford, I. Freimer, N.A. Gao, H. Giegling, I. Gillespie, N.A. Gordon, S.D. Gottesman, R.F. Griswold, M.E. Gudnason, V. Harris, T.B. Hartmann, A.M. Hatzimanolis, A. Heiss, G. Holliday, E.G. Joshi, P.K. Kähönen, M. Kardia, S.L.R. Karlsson, I. Kleineidam, L. Knopman, D.S. Kochan, N.A. Konte, B. Kwok, J.B. Le Hellard, S. Lee, T. Lehtimäki, T. Li, S.-C. Lill, C.M. Liu, T. Koini, M. London, E. Longstreth, W.T., Jr. Lopez, O.L. Loukola, A. Luck, T. Lundervold, A.J. Lundquist, A. Lyytikäinen, L.-P. Martin, N.G. Montgomery, G.W. Murray, A.D. Need, A.C. Noordam, R. Nyberg, L. Ollier, W. Papenberg, G. Pattie, A. Polasek, O. Poldrack, R.A. Psaty, B.M. Reppermund, S. Riedel-Heller, S.G. Rose, R.J. Rotter, J.I. Roussos, P. Rovio, S.P. Saba, Y. Sabb, F.W. Sachdev, P.S. Satizabal, C.L. Schmid, M. Scott, R.J. Scult, M.A. Simino, J. Slagboom, P.E. Smyrnis, N. Soumaré, A. Stefanis, N.C. Stott, D.J. Straub, R.E. Sundet, K. Taylor, A.M. Taylor, K.D. Tzoulaki, I. Tzourio, C. Uitterlinden, A. Vitart, V. Voineskos, A.N. Kaprio, J. Wagner, M. Wagner, H. Weinhold, L. Wen, K.H. Widen, E. Yang, Q. Zhao, W. Adams, H.H.H. Arking, D.E. Bilder, R.M. Bitsios, P. Boerwinkle, E. Chiba-Falek, O. Corvin, A. De Jager, P.L. Debette, S. Donohoe, G. Elliott, P. Fitzpatrick, A.L. Gill, M. Glahn, D.C. Hägg, S. Hansell, N.K. Hariri, A.R. Ikram, M.K. Jukema, J.W. Vuoksimaa, E. Keller, M.C. Kremen, W.S. Launer, L. Lindenberger, U. Palotie, A. Pedersen, N.L. Pendleton, N. Porteous, D.J. Räikkönen, K. Raitakari, O.T. Ramirez, A. Reinvang, I. Rudan, I. Dan Rujescu Schmidt, R. Schmidt, H. Schofield, P.W. Schofield, P.R. Starr, J.M. Steen, V.M. Trollor, J.N. Turner, S.T. Van Duijn, C.M. Villringer, A. Weinberger, D.R. Weir, D.R. Wilson, J.F. Malhotra, A. McIntosh, A.M. Gale, C.R. Seshadri, S. Mosley, T.H., Jr. Bressler, J. Lencz, T. Deary, I.J.

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article. © 2019, The Author(s).

Published
2019

5. Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways

Author

Lam, M. Hill, W.D. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Stahl, E. Huckins, L. Liewald, D.C. Djurovic, S. Melle, I. Sundet, K. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Hartmann, A.M. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Attix, D.K. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Arking, D.E. Smyrnis, N. Bilder, R.M. Freimer, N.A. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Malhotra, A.K. Lencz, T.

Subjects
mental disorders
Abstract

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive (“discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms—early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways—that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness. © 2019

Published
2019

6. Multi-Trait analysis of gwas and biological insights into cognition: A response to hill (2018)

Author

Lam, M. Trampush, J.W. Yu, J. Knowles, E. Djurovic, S. Melle, I. Sundet, K. Christoforou, A. Reinvang, I. Derosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Attix, D.K. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Arking, D.E. Smyrnis, N. Bilder, R.M. Freimer, N.A. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Hellard, S.L. Keller, M.C. Andreassen, O.A. Glahn, D.C. Malhotra, A.K. Lencz, T.

Abstract

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'. © The Author(s) 2018Â.

Published
2018

7. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author

Savage, J.E. Jansen, P.R. Stringer, S. Watanabe, K. Bryois, J. De Leeuw, C.A. Nagel, M. Awasthi, S. Barr, P.B. Coleman, J.R.I. Grasby, K.L. Hammerschlag, A.R. Kaminski, J.A. Karlsson, R. Krapohl, E. Lam, M. Nygaard, M. Reynolds, C.A. Trampush, J.W. Young, H. Zabaneh, D. Hägg, S. Hansell, N.K. Karlsson, I.K. Linnarsson, S. Montgomery, G.W. Muñoz-Manchado, A.B. Quinlan, E.B. Schumann, G. Skene, N.G. Webb, B.T. White, T. Arking, D.E. Avramopoulos, D. Bilder, R.M. Bitsios, P. Burdick, K.E. Cannon, T.D. Chiba-Falek, O. Christoforou, A. Cirulli, E.T. Congdon, E. Corvin, A. Davies, G. Deary, I.J. Derosse, P. Dickinson, D. Djurovic, S. Donohoe, G. Conley, E.D. Eriksson, J.G. Espeseth, T. Freimer, N.A. Giakoumaki, S. Giegling, I. Gill, M. Glahn, D.C. Hariri, A.R. Hatzimanolis, A. Keller, M.C. Knowles, E. Koltai, D. Konte, B. Lahti, J. Le Hellard, S. Lencz, T. Liewald, D.C. London, E. Lundervold, A.J. Malhotra, A.K. Melle, I. Morris, D. Need, A.C. Ollier, W. Palotie, A. Payton, A. Pendleton, N. Poldrack, R.A. Räikkönen, K. Reinvang, I. Roussos, P. Rujescu, D. Sabb, F.W. Scult, M.A. Smeland, O.B. Smyrnis, N. Starr, J.M. Steen, V.M. Stefanis, N.C. Straub, R.E. Sundet, K. Tiemeier, H. Voineskos, A.N. Weinberger, D.R. Widen, E. Yu, J. Abecasis, G. Andreassen, O.A. Breen, G. Christiansen, L. Debrabant, B. Dick, D.M. Heinz, A. Hjerling-Leffler, J. Ikram, M.A. Kendler, K.S. Martin, N.G. Medland, S.E. Pedersen, N.L. Plomin, R. Polderman, T.J.C. Ripke, S. Van Der Sluis, S. Sullivan, P.F. Vrieze, S.I. Wright, M.J. Posthuma, D.

Abstract

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. © 2018 The Author(s).

Published
2018

8. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium (vol 22, pg 336, 2017)

Author

Trampush, JW, Yang, MLZ, Yu, J, Knowles, E, Davies, G, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Raikkonen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, DK, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Arking, DE, Smyrnis, N, Bilder, RM, Freimer, NA, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Malhotra, AK, and Lencz, T

Subjects
Psychiatry, 17 Psychology And Cognitive Sciences, Biochemistry & Molecular Biology, Science & Technology, Neurosciences, Neurosciences & Neurology, 11 Medical And Health Sciences, 06 Biological Sciences, Life Sciences & Biomedicine
Published
2017

9. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

Author

Trampush, J. W. Yang, M. L. Z. Yu, J. Knowles, E. and Davies, G. Liewald, D. C. Starr, J. M. Djurovic, S. and Melle, I. Sundet, K. Christoforou, A. Reinvang, I. and DeRosse, P. Lundervold, A. J. Steen, V. M. Espeseth, T. and Raikkonen, K. Widen, E. Palotie, A. Eriksson, J. G. and Giegling, I. Konte, B. Roussos, P. Giakoumaki, S. and Burdick, K. E. Payton, A. Ollier, W. Horan, M. and Chiba-Falek, O. Attix, D. K. Need, A. C. Cirulli, E. T. and Voineskos, A. N. Stefanis, N. C. Avramopoulos, D. and Hatzimanolis, A. Arking, D. E. Smyrnis, N. Bilder, R. M. and Freimer, N. A. Cannon, T. D. London, E. Poldrack, R. A. and Sabb, F. W. Congdon, E. Conley, E. D. Scult, M. A. and Dickinson, D. Straub, R. E. Donohoe, G. Morris, D. and Corvin, A. Gill, M. Hariri, A. R. Weinberger, D. R. and Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M. C. Andreassen, O. A. Deary, I. J. and Glahn, D. C. Malhotra, A. K. Lencz, T.

Abstract

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P

Published
2017

10. Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

Author

Lam, M. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Liewald, D.C. Starr, J.M. Djurovic, S. Melle, I. Sundet, K. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Attix, D.K. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Arking, D.E. Smyrnis, N. Bilder, R.M. Freimer, N.A. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Malhotra, A.K. Lencz, T.

Abstract

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability (“g”), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth. Lam et al. conduct a large-scale genome-wide association study of cognitive ability, identifying 70 associated loci. Results provide biological insights into the molecular basis of individual differences in cognitive ability, as well as their relationship to psychiatric and other health-relevant phenotypes. © 2017 The Author(s)

Published
2017

11. A Genome-wide association study of non-pathological cognitive ageing

Author

Davies, G, Harris, S, Reynolds, C, Payton, A, Liewald, D, Lopez, L, Luciano, M, Gow, A, Corley, J, Henderson, R, Murray, C, Pattie, A, Fox, H, Redmond, P, Lutz, M, Chiba-Falek, O, Linnertz, C, Saith, S, Knight, H, Haggarty, P, McNeill, G, Ollier, W, Horan, M, Roses, A, and Ponting, C

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results