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28 results on '"Straub, R.E."'

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 (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

4. 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

5. 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., 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., 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., Rujescu, D., 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., Bressler, J., Lencz, T., Deary, I.J., 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., 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., Rujescu, D., 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., Bressler, J., Lencz, T., and Deary, I.J.

Abstract

These authors contributed equally: Gail Davies, Max Lam. These authors jointly supervised this work: Todd Lencz, Ian J. Deary.

Published
2019

6. Publisher Correction: Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment

Author

Scheggia, D., Mastrogiacomo, R., Mereu, M., Sannino, S., Straub, R.E., Armando, M., Managò, F., Guadagna, S., Piras, F., Zhang, F., Kleinman, J.E., Hyde, T.M., Kaalund, S.S., Pontillo, M., Orso, G., Caltagirone, C., Borrelli, E., De Luca, M.A., Vicari, S., Weinberger, D.R., Spalletta, G., and Papaleo, F.

Abstract

In the original version of this Article, references in the Methods section incorrectly referred to references in the Supplementary References section. The relevant references (now numbered 20, 27, 42, 47, 69-80) have been removed from the Supplementary References section of the Supplementary Information file and added to the References section of the main manuscript, in both the PDF and HTML versions of the Article.

Published
2018

7. 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

8. 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

9. Age at first birth in women is genetically associated with increased risk of schizophrenia

Author

Ni, G. (Guiyan), Gratten, J. (Jacob), Wray, N.R. (Naomi R.), Lee, S.H. (Sang Hong), Ripke, S. (Stephan), Neale, B.M. (Benjamin), Corvin, A. (Aiden), Walters, J.T. (James), Farh, K.-H. (Kai-How), Holmans, P.A. (Peter A.), Lee, P.H. (Phil H.), Bulik-Sullivan, B.K. (Brendan), Collier, D.A. (David), Huang, H. (Hailiang), Pers, T.H. (Tune), Agartz, I. (Ingrid), Agerbo, E. (Esben), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Bacanu, S.A. (Silviu), Begemann, M. (Martin), Belliveau, R.A. (Richard A.), Bene, J. (Judit), Bergen, S.E. (Sarah), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan J.), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Chan, R.C.K. (Raymond C. K.), Chen, R.Y.L. (Ronald Y.), Chen, E.Y.H. (Eric Y. H.), Cheng, W. (Wei), Cheung, E.F.C. (Eric F. C.), Chong, S.A. (Siow Ann), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cohen, N. (Nadine), Cormican, P. (Paul), Craddock, N.J. (Nick), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Demontis, D. (Ditte), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Durmishi, N. (Naser), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedl, M., Friedman, J.I. (Joseph), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Golimbet, V. (Vera), Gopal, R. (Robin), Haan, L. (Lieuwe) de, Hammer, C. (Christian), Hamshere, M.L. (Marian), Hansen, M. (Mark), Hansen, T. (Thomas), Haroutunian, V. (Vahram), Hartmann, A.M. (Annette M.), Henskens, F.A. (Frans), Herms, S. (Stefan), Hirschhorn, J.N. (Joel), Hoffmann, P. (Per), Hofman, A. (Andrea), Hollegaard, M.V. (Mads V), Hougaard, D.M. (David), Ikeda, M. (Masashi), Joa, I. (Inge), Juliá, A. (Antonio), Kahn, R. (René), Kalaydjieva, L. (Luba), Karachanak-Yankova, S. (Sena), Karjalainen, J. (Juha), Kavanagh, D. (David), Keller, M.C. (Matthew C), Kennedy, J.L., Khrunin, A. (Andrey), Kim, Y. (Yunjung), Klovins, J. (Janis), Knowles, J.A. (James A), Konte, B. (Bettina), Kučinskas, V. (Vaidutis), Kucinskiene, Z.A. (Zita Ausrele), Kuzelova-Ptackova, H. (Hana), Kähler, J. (Jan), Laurent, C. (Camille), Keong, J.L.C. (Jimmy Lee Chee), Legge, S.E. (Sophie), Lerer, B. (Bernard), Li, M. (Miaoxin), Li, T. (Tao), Liang, K.-Y. (Kung-Yee), Lieberman, A.P. (Andrew), Limborska, S. (Svetlana), Loughland, C.M. (Carmel), Lubinski, J. (Jan), Lönnqvist, J. (Jouko), Macek, M. (Milan MI), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Marsal, S. (Sara), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melegh, B. (Bela), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W.), Mors, O., Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Müller-Myhsok, B. (B.), Nelis, M. (Mari), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nikitina-Zake, L. (Liene), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), O'neill, F.A. (F. Anthony), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), Os, J.V. (Jim Van), Pantelis, C. (Christos), Papadimitriou, G.N. (George), Papiol, S. (Sergi), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Pejovic-Milovancevic, M. (Milica), Perkins, D.O. (Diana O.), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Schall, J.D. (Jeffrey), Schubert, C.R. (Christian R.), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney J.), Seidman, L.J. (Larry), Shi, J. (Jianxin), Sigurdsson, E. (Engilbert), Silagadze, T. (Teimuraz), Silverman, J.M. (Jeremy M.), Sim, K. (Kang), Slominsky, P. (Petr), Smoller, J.W., So, H.-C. (Hon-Cheong), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Stogmann, E. (Elisabeth), Straub, R.E. (Richard), Strengman, E. (Eric), Strohmaier, J. (Jana), Stroup, T.S. (T. Scott), Subramaniam, V. (Venkat), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Söderman, E. (Erik), Thirumalai, S. (Srinivasa), Toncheva, D. (Draga), Tosato, S. (Sarah), Veijola, J. (Juha), Waddington, J. (John), Walsh, D. (Dermot), Wang, D. (Dai), Wang, Q. (Qiang), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wong, E.H.M. (Emily H.M.), Wormley, B.K. (Brandon K.), Xi, H.S. (Hualin Simon), Zai, C.C. (Clement C.), Zheng, X. (Xuebin), Zimprich, F. (Fritz), Zwart, J-A. (John-Anker), Visscher, P.M. (Peter), Adolfsson, R., Andreassen, O.A. (Ole), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D.), Borglum, A.D. (Anders), Cichon, S. (Sven), Darvasi, A. (Ariel), Domenici, E. (Enrico), Ehrenreich, H. (Hannelore), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Lencz, T. (Todd), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), Liu, J. (Jianjun), Malhotra, A.K. (Anil K), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L.), Mortensen, P.B., Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey L.), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sham, P.C. (Pak C.), Sklar, P. (Pamela), Clair, D.S., Weinberger, D.R. (Daniel), Wendland, A. (Annika), Werge, T.M. (Thomas), Daly, M.J. (Mark J.), Sullivan, P.F. (Patrick), O'donovan, M.C. (Michael), Ni, G. (Guiyan), Gratten, J. (Jacob), Wray, N.R. (Naomi R.), Lee, S.H. (Sang Hong), Ripke, S. (Stephan), Neale, B.M. (Benjamin), Corvin, A. (Aiden), Walters, J.T. (James), Farh, K.-H. (Kai-How), Holmans, P.A. (Peter A.), Lee, P.H. (Phil H.), Bulik-Sullivan, B.K. (Brendan), Collier, D.A. (David), Huang, H. (Hailiang), Pers, T.H. (Tune), Agartz, I. (Ingrid), Agerbo, E. (Esben), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Bacanu, S.A. (Silviu), Begemann, M. (Martin), Belliveau, R.A. (Richard A.), Bene, J. (Judit), Bergen, S.E. (Sarah), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan J.), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Chan, R.C.K. (Raymond C. K.), Chen, R.Y.L. (Ronald Y.), Chen, E.Y.H. (Eric Y. H.), Cheng, W. (Wei), Cheung, E.F.C. (Eric F. C.), Chong, S.A. (Siow Ann), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cohen, N. (Nadine), Cormican, P. (Paul), Craddock, N.J. (Nick), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Demontis, D. (Ditte), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Durmishi, N. (Naser), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedl, M., Friedman, J.I. (Joseph), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Golimbet, V. (Vera), Gopal, R. (Robin), Haan, L. (Lieuwe) de, Hammer, C. (Christian), Hamshere, M.L. (Marian), Hansen, M. (Mark), Hansen, T. (Thomas), Haroutunian, V. (Vahram), Hartmann, A.M. (Annette M.), Henskens, F.A. (Frans), Herms, S. (Stefan), Hirschhorn, J.N. (Joel), Hoffmann, P. (Per), Hofman, A. (Andrea), Hollegaard, M.V. (Mads V), Hougaard, D.M. (David), Ikeda, M. (Masashi), Joa, I. (Inge), Juliá, A. (Antonio), Kahn, R. (René), Kalaydjieva, L. (Luba), Karachanak-Yankova, S. (Sena), Karjalainen, J. (Juha), Kavanagh, D. (David), Keller, M.C. (Matthew C), Kennedy, J.L., Khrunin, A. (Andrey), Kim, Y. (Yunjung), Klovins, J. (Janis), Knowles, J.A. (James A), Konte, B. (Bettina), Kučinskas, V. (Vaidutis), Kucinskiene, Z.A. (Zita Ausrele), Kuzelova-Ptackova, H. (Hana), Kähler, J. (Jan), Laurent, C. (Camille), Keong, J.L.C. (Jimmy Lee Chee), Legge, S.E. (Sophie), Lerer, B. (Bernard), Li, M. (Miaoxin), Li, T. (Tao), Liang, K.-Y. (Kung-Yee), Lieberman, A.P. (Andrew), Limborska, S. (Svetlana), Loughland, C.M. (Carmel), Lubinski, J. (Jan), Lönnqvist, J. (Jouko), Macek, M. (Milan MI), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Marsal, S. (Sara), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melegh, B. (Bela), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W.), Mors, O., Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Müller-Myhsok, B. (B.), Nelis, M. (Mari), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nikitina-Zake, L. (Liene), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), O'neill, F.A. (F. Anthony), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), Os, J.V. (Jim Van), Pantelis, C. (Christos), Papadimitriou, G.N. (George), Papiol, S. (Sergi), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Pejovic-Milovancevic, M. (Milica), Perkins, D.O. (Diana O.), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Schall, J.D. (Jeffrey), Schubert, C.R. (Christian R.), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney J.), Seidman, L.J. (Larry), Shi, J. (Jianxin), Sigurdsson, E. (Engilbert), Silagadze, T. (Teimuraz), Silverman, J.M. (Jeremy M.), Sim, K. (Kang), Slominsky, P. (Petr), Smoller, J.W., So, H.-C. (Hon-Cheong), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Stogmann, E. (Elisabeth), Straub, R.E. (Richard), Strengman, E. (Eric), Strohmaier, J. (Jana), Stroup, T.S. (T. Scott), Subramaniam, V. (Venkat), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Söderman, E. (Erik), Thirumalai, S. (Srinivasa), Toncheva, D. (Draga), Tosato, S. (Sarah), Veijola, J. (Juha), Waddington, J. (John), Walsh, D. (Dermot), Wang, D. (Dai), Wang, Q. (Qiang), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wong, E.H.M. (Emily H.M.), Wormley, B.K. (Brandon K.), Xi, H.S. (Hualin Simon), Zai, C.C. (Clement C.), Zheng, X. (Xuebin), Zimprich, F. (Fritz), Zwart, J-A. (John-Anker), Visscher, P.M. (Peter), Adolfsson, R., Andreassen, O.A. (Ole), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D.), Borglum, A.D. (Anders), Cichon, S. (Sven), Darvasi, A. (Ariel), Domenici, E. (Enrico), Ehrenreich, H. (Hannelore), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Lencz, T. (Todd), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), Liu, J. (Jianjun), Malhotra, A.K. (Anil K), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L.), Mortensen, P.B., Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey L.), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sham, P.C. (Pak C.), Sklar, P. (Pamela), Clair, D.S., Weinberger, D.R. (Daniel), Wendland, A. (Annika), Werge, T.M. (Thomas), Daly, M.J. (Mark J.), Sullivan, P.F. (Patrick), and O'donovan, M.C. (Michael)

Abstract

Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia

Published
2018
Full Text
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10. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), Deary, I.J. (Ian), Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), and Deary, I.J. (Ian)

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the c

Published
2018
Full Text
View/download PDF

11. 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., 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, Liu, T., Koini, M., London, E., Longstreth, W.T., 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., Rujescu, D., 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, Arno, 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., Deary, I.J., 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, Liu, T., Koini, M., London, E., Longstreth, W.T., 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., Rujescu, D., 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, Arno, 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.

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16–102) and find 148 genome-wide significant independent loci (P < 5 × 10−8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018

12. 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

13. Schizophrenia candidate gene ERBB4: Covert routes of vulnerability to psychosis detected at the population level

Author

Stefanis, N.C. Hatzimanolis, A. Smyrnis, N. Avramopoulos, D. Evdokimidis, I. Van Os, J. Stefanis, C.N. Straub, R.E. Weinberger, D.R.

Abstract

Prior genetic and functional evidence established ERBB4 as a probable schizophrenia susceptibility gene that may confer risk via modulating brain information processing dependent on the integrity of frontotemporal brain circuitry. Utilizing retrospective data drawn from the cross-sectional population-based Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS) (n = 1127), we attempted to independently replicate and further extend previous findings by examining the effects of ERBB4 gene variants on 3 broad population-based psychosis-related phenotypes: verbal working memory (VWM), trait schizotypy, and stress-induced subclinical psychotic experiences (PE). Three common ERBB4 single nucleotide polymorphisms that were previously associated with schizophrenia and impaired frontotemporal-related information processing (rs7598440, rs839523, and rs707284), their haplotypes, and corresponding diplotypes were tested. VWM performance was significantly associated with rs839523 and rs707284 markers even after correction for multiple testing, thus validating reported findings that have implicated ERBB4 gene variation on working memory. No associations were detected between these ERBB4 variants and trait schizotypy. However, we were able to detect a significant effect of rs7598440 marker on PE expressed under stressful environmental conditions. Combined haplotype analysis of the above 3 markers, identified a yin-yang pattern of association, confirmed at the diplotype level. While GGG haplotype homozygotes were associated with protective effects on VWM performance and PE, AAA risk haplotype carriers were associated with worse VWM performance and simultaneously exhibited significantly elevated PE. This dual, possibly pleiotropic, impact on frontotemporal circuitry and increased sensitivity to psychosocial stress may represent subtle manifestations of ERBB4-related vulnerability to psychosis, expressed at the population level. © 2013 The Author.

Published
2013

14. Variation in psychosis gene ZNF804A is associated with a refined schizotypy phenotype but not neurocognitive performance in a large young male population

Author

Stefanis, N.C. Hatzimanolis, A. Avramopoulos, D. Smyrnis, N. Evdokimidis, I. Stefanis, C.N. Weinberger, D.R. Straub, R.E.

Abstract

Genetic variability within the ZNF804A gene has been recently found to be associated with schizophrenia and bipolar disorder, although the pathways by which this gene may confer risk remain largely unknown. We set out to investigate whether common ZNF804A variants affect psychosis-related intermediate phenotypes such as cognitive performance dependent on prefrontal and frontotemporal brain function, schizotypal traits, and attenuated psychotic experiences in a large young male population. Association analyses were performed using all 4 available self-rated schizotypy questionnaires and cognitive data retrospectively drawn from the Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS). DNA samples from 1507 healthy young men undergoing induction to military training were genotyped for 4 previously studied polymorphic markers in the ZNF804A gene locus. Single-marker analysis revealed significant associations between 2 recently identified candidate schizophrenia susceptibility variants (rs1344706 and rs7597593) and a refined positive schizotypy phenotype characterized primarily by self-rated paranoia/ideas of reference. Nominal associations were noted with all positive, but not negative, schizotypy related factors. ZNF804A genotype effect on paranoia was confirmed at the haplotype level. No significant associations were noted with central indexes of sustained attention or working memory performance. In this study, ZNF804A variation was associated with a population-based self-rated schizotypy phenotype previously suggested to preferentially reflect genetic liability to psychosis and defined by a tendency to misinterpret otherwise neutral social cues and perceptual experiences in one's immediate environment, as personally relevant and significant information. This suggests a novel route by which schizophrenia-implicated ZNF804A genetic variation may confer risk to clinical psychosis at the general population level. © 2012 The Author.

Published
2013

15. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia

Author

Chumakov, I. (Ilya), Blumenfeld, M. (Marta), Guerassimenko, O. (Oxana), Cavarec, L. (Laurent), Palicio, M. (Marta), Abderrahim, H. (Hadi), Bougueleret, L. (Lydie), Barry, C. (Caroline), Tanaka, H. (Hiroaki), Rosa, P. (Philippe) La, Puech, A. (Anne), Tahri, N. (Nadia), Cohen-Akenine, A. (Annick), Delabrosse, S. (Sylvain), Lissarrague, S. (Sébastien), Picard, F.P., Maurice, K. (Karelle), Essioux, L. (Laurent), Millasseau, P. (Philippe), Grel, P. (Pascale), Debailleul, V. (Virginie), Simon, A-M. (Anne-Marie), Caterina, D. (Dominique), Dufaure, I. (Isabelle), Malekzadeh, K. (Kattayoun), Belova, M. (Maria), Luan, J.J., Bouillot, M. (Michel), Sambucy, J.L., Primas, G. (Gwenael), Saumier, M. (Martial), Boubkiri, N. (Nadia), Martin-Saumier, S. (Sandrine), Nasroune, M. (Myriam), Peixoto, H. (Hélène), Delaye, A. (Arnaud), Pinchot, V. (Virginie), Bastucci, M. (Mariam), Guillou, S. (Sophie), Chevillon, M. (Magali), Sainz-Fuertes, R. (Ricardo), Meguenni, S. (Said), Aurich-Costa, J. (Joan), Cherif, D. (Dorra), Gimalac, A. (Anne), Duijn, C.M. (Cornelia) van, Gauvreau, D. (Denis), Ouelette, G., Fortier, I. (Isabel), Realson, J., Sherbatich, T. (Tatiana), Riazanskaia, N. (Nadejda), Rogaev, E. (Evgeny), Raeymaekers, P. (Peter), Aerssens, J. (Jeroen), Konings, F. (Frank), Luyten, W. (Walter), Macciardi, F. (Fabio), Sham, P.C. (Pak), Straub, R.E. (Richard), Weinberger, D.R. (Daniel), Cohen, N. (Nadine), Cohen, D. (Daniel), Chumakov, I. (Ilya), Blumenfeld, M. (Marta), Guerassimenko, O. (Oxana), Cavarec, L. (Laurent), Palicio, M. (Marta), Abderrahim, H. (Hadi), Bougueleret, L. (Lydie), Barry, C. (Caroline), Tanaka, H. (Hiroaki), Rosa, P. (Philippe) La, Puech, A. (Anne), Tahri, N. (Nadia), Cohen-Akenine, A. (Annick), Delabrosse, S. (Sylvain), Lissarrague, S. (Sébastien), Picard, F.P., Maurice, K. (Karelle), Essioux, L. (Laurent), Millasseau, P. (Philippe), Grel, P. (Pascale), Debailleul, V. (Virginie), Simon, A-M. (Anne-Marie), Caterina, D. (Dominique), Dufaure, I. (Isabelle), Malekzadeh, K. (Kattayoun), Belova, M. (Maria), Luan, J.J., Bouillot, M. (Michel), Sambucy, J.L., Primas, G. (Gwenael), Saumier, M. (Martial), Boubkiri, N. (Nadia), Martin-Saumier, S. (Sandrine), Nasroune, M. (Myriam), Peixoto, H. (Hélène), Delaye, A. (Arnaud), Pinchot, V. (Virginie), Bastucci, M. (Mariam), Guillou, S. (Sophie), Chevillon, M. (Magali), Sainz-Fuertes, R. (Ricardo), Meguenni, S. (Said), Aurich-Costa, J. (Joan), Cherif, D. (Dorra), Gimalac, A. (Anne), Duijn, C.M. (Cornelia) van, Gauvreau, D. (Denis), Ouelette, G., Fortier, I. (Isabel), Realson, J., Sherbatich, T. (Tatiana), Riazanskaia, N. (Nadejda), Rogaev, E. (Evgeny), Raeymaekers, P. (Peter), Aerssens, J. (Jeroen), Konings, F. (Frank), Luyten, W. (Walter), Macciardi, F. (Fabio), Sham, P.C. (Pak), Straub, R.E. (Richard), Weinberger, D.R. (Daniel), Cohen, N. (Nadine), and Cohen, D. (Daniel)

Abstract

A map of 191 single-nucleotide polymorphism (SNPs) was built across a 5-Mb segment from chromosome 13q34 that has been genetically linked to schizophrenia. DNA from 213 schizophrenic patients and 241 normal individuals from Canada were genotyped with this marker set. Two 1,400- and 65-kb regions contained markers associated with the disease. Two markers from the 65-kb region were also found to be associated to schizophrenia in a Russian sample. Two overlapping genes G72 and G30 transcribed in brain were experimentally annotated in this 65-kb region. Transfection experiments point to the existence of a 153-aa protein coded by the G72 gene. This protein is rapidly evolving in primates, is localized to endoplasmic reticulum/Golgi in transfected cells, is able to form multimers and specifically binds to carbohydrates. Yeast two-hybrid experiments with the G72 protein identified the enzyme d-amino acid oxidase (DAAO) as an interacting partner. DAAO is expressed in human brain where it oxidizes d-serine, a potent activator of N-methyl-D-aspartate type glutamate receptor. The interaction between G72 and DAAO was confirmed in vitro and resulted in activation of DAAO. Four SNP markers from DAAO were found to be associated with schizophrenia in the Canadian samples. Logistic regression revealed genetic interaction between associated SNPs in vicinity of two genes. The association of both DAAO and a new gene G72 from 13q34 with schizophrenia together with activation of DAAO activity by a G72 protein product points to the involvement of this N-methyl-d-aspartate receptor regulation pathway in schizophrenia.

Published
2002
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20. Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia.

Author

Hashimoto, R., Straub, R.E., Weickert, C.S., Hyde, T.M., Kleinman, J.E., and Weinberger, D.R.

Subjects
*LINKAGE (Genetics), *GENE expression, *PREFRONTAL cortex, *SCHIZOPHRENIA, *CYCLOPHILINS, *ALLELES
Abstract

Genetic linkage and association have implicated neuregulin-1 (NRG-1) as a schizophrenia susceptibility gene. We measured mRNA expression levels of the three major isoforms of NRG-1 (ie type I, type II, and type III) in the postmortem dorsolateral prefrontal cortex (DLPFC) from matched patients and controls using real-time quantitative RT-PCR. Expression levels of three internal controls-GAPDH, cyclophilin, and ß-actin-were unchanged in schizophrenia, and there were no changes in the absolute levels of the NRG-1 isoforms. However, type I expression normalized by GAPDH levels was significantly increased in schizophrenia DLPFC (by 23%) and positively correlated with antipsychotic medication dosage. Type II/type I and type II/type III ratios were significantly decreased (18 and 23% respectively). There was no effect on the NRG-1 mRNA levels of genotype at two SNPs previously associated with schizophrenia, suggesting that these alleles are not functionally responsible for abnormal NRG-1 expression patterns in patients. Subtle abnormalities in the expression patterns of NRG-1 mRNA isoforms in DLPFC may be associated with schizophrenia.Molecular Psychiatry (2004) 9, 299-307. doi:10.1038/sj.mp.4001434 [ABSTRACT FROM AUTHOR]

Published
2004
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21. Genome-wide scans of three independent sets of 90 Irish mutiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes.

Author

Straub, R.E., MacLean, C.J., Ma, Y., Webb, B.T., Myakishev, M.V., Harris-Kerr, C., Wormley, B., Sadek, H., Kadambi, B., O'Neill, F.A., Walsh, D., and Kendler, K.S.

Subjects
*GENETICS of schizophrenia, *HUMAN genome, *DISEASE susceptibility, *IRISH people, *DISEASES
Abstract

From our linkage study of irish families with a high density of schizophrenia, we have previously reported evidence for susceptibility genes in regions 5q21-31, 6p24-21, 8p22-21, and 10p15-p11. In this report, we describe the cumulative results from independent genome scans of three a priori random subsets of 90 families each, and from multipoint analysis of all 270 families in ten regions. Of these ten regions, three (13q32, 18p11-q11, and 18q22-23) did not generate scores above the empirical baseline pairwise scan results, and one (6q13-26) generated a weak signal. Six other regions produced more positive pairwise and multipoint results. They showed the following maximum multipoint H-LOD (heterogeneity LOD) and NPL scores: 2p14-13:0.89 (P = 0.06) and 2.08 (P = 0.02), 4q24-32:1.84 (P = 0.007) and 1.67 (P = 0.03), 5q21-31:2.88 (P=0.0007), and 2.65 (P=0.002), 6p25-24:2.13 (P = 0.005) and 3.59 (P=0.0005), 6p23:2.42 (P = 0.001) and 3.07 (P = 0.001), 8p22-21:1.57 (P = 0.01) and 2.56 (P = 0.005), 10p1511:2.04 (P = 0.005) and 1.78 (P = 0.03). The degree of 'internal replication' across subsets differed, with 5q, 6p, and 8p being most consistent and 2p and 10p being least consistent. On 6p, the data suggested the presence of two susceptibility genes, in 6p25-24 and 6p23-22. Very few families were positive on more than one region, and little correlation between regions was evident, suggesting substantial locus heterogeneity. The levels of statistical significance were modest, as expected from loci contributing to complex traits. However, our internal replications, when considered along with the positive results obtained in multiple other samples, suggests that most of these six regions are likely to contain genes that influence liability to schizophrenia. [ABSTRACT FROM AUTHOR]

Published
2002
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22. Susceptibility genes for nicotine dependence: a genome scan and followup in an independent sample suggest that regions on chromosomes 2, 4, 10, 16, 17 and 18 merit further study.

Author

Straub, R.E., Sullivan, P.F., Ma, Y., Myakishev, M.V., Harris-Kerr, C., Wormley, B., Kadambi, B., Sadek, H., Silverman, M.A., Webb, B.T., Neale, M.C., Bulik, C.M., Joyce, P.R., and Kendler, K.S.

Subjects
*NICOTINE, *SMOKING, *LINKAGE (Genetics)
Abstract

Cigarette smoking is associated with considerable morbidity, mortality, and public health costs. Genetic factors influence both smoking initiation and nicotine dependence, but none of the genes involved have been identified. A genome scan using 451 markers was conducted to identify chromosomal regions linked to nicotine dependence in a collection of 130 families containing 343 genotyped individuals (308 nicotine-dependent) from Christchurch, New Zealand. By pairwise analysis, the best result was with marker D2S1326 which gave a Iod score under heterogeneity (H-LOD) of 2.63 (P=0.0012) and a nonparametric linkage (NPL, Z[sub all]) score of 2.65 (P=0.0011). To identify regions that warranted further study, rather than comparing the pairwise scores from the scan to theoretical thresholds, we compared them to an empirical baseline, found here to be H-LOD scores of 0.5 and Z[sub all] scores of 1.0. We also found a number of large (31-88 cM) regions where many (8-16) consecutive markers yielded small but positive Z[sub all] scores. Selected regions of chromosomes 2, 4, 10, 16, 17 and 18 were investigated further by additional genotyping of the Christchurch sample and an independent sample from Richmond, Virginia (91 families with 264 genotyped individuals, 211 nicotine-dependent). Multipoint nonparametric analysis showed the following maximums for the Christchurch sample: Chr. 2 (Z[sub lr]=2.61, P=0.005), Chr. 4 (Z[sub lr]=1.36, P=0.09), Chr. 10 (Z[sub lr]=2.43, P=0.008), Chr. 16 (Z[sub lr]=0.85, P=0.19), Chr. 17 (Z[sub lr]=1.64, P=0.05), Chr. 18 (Z[sub lr]=1.54, P=0.06). Analysis of the Richmond sample showed the following maximums: Chr. 2 (Z[sub lr]=1.00, P=0.15), Chr. 4 (Z[sub lr]=0.39, P=0.34), Chr. 10 (Z[sub lr]=1.21, P=0.11), Chr. 16 (Z[sub lr]=1.11, P=0.13), Chr. 17 (Z[sub lr]=1.60, P=0.05), Chr. 18 (Z[sub lr]=1.33, P=0.09). It is probable that the small samples used here provided only limited power to detect linkage. It may have been difficult therefore to... [ABSTRACT FROM AUTHOR]

Published
1999
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23. No evidence to support the association of the potassium channel gene hSKCa3 CAG repeat with schizophrenia or bipolar disorder in the Irish population.

Author

Hawi, Z., Mynett-Johnson, L., Murphy, V., Straub, R.E., Kendler, K.S., Walsh, D, McKeon, P., and Gill, M.

Subjects
MENTAL illness genetics, GENETICS of schizophrenia, POTASSIUM channels
Abstract

Anticipation has attracted much interest and has been demonstrated in several neuropsychiatric disorders. For some disorders, this phenomenon has been found to correlate with the repeat number in large and unstable repeats (CAG/CTG). In addition, case control studies have suggested an increase in triplet repeat size in the psychoses. Recently, it was reported that the larger alleles (longer than 19 repeats) of the second potassium channel gene hSKCa3 are associated with schizophrenia in European and American samples. A similar trend, though not statistically significant, was also seen in bipolar disorder samples. This was further supported by an independent UK study. In this investigation, we have examined Irish familial schizophrenic patients, bipolar affective disorder patients and ethnically matched controls in an effort to replicate these findings. No significant differences between the patients and the control groups were observed. In addition, linkage analyses in the multiplex schizophrenic families showed no evidence for linkage or linkage disequilibrium. We concluded that the polymorphism of the second CAG repeat of the hSKCa3 gene is not a risk factor in schizophrenia or bipolar disorder, at least in the Irish population. [ABSTRACT FROM AUTHOR]

Published
1999
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24. Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families.

Author

Straub, R.E., MacLean, C.J., O'Neill, F.A., Walsh, D., and Kendler, K.S.

Subjects
*GENETICS of schizophrenia, *CHROMOSOME abnormalities
Abstract

In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region appears to be distinct from those chromosome 5 regions studied in two prior reports, but the same as that producing positive results in the report by Wildenauer and colleagues found elsewhere in this issue. The largest pairwise heterogeneity LOD (H-LOD) score was found with marker DSS393 (max 3.04, P = 0.0005), assuming a narrow phenotypic category, and a genetic model with intermediate heterozygotic liability. In marked contrast to the H-LOD scores from our sample with markers from the regions of interest on chromosomes 6p[sup 4] and 8p, expanding the disease definition to include schizophrenia spectrum or nonspectrum disorders produced substantially smaller scores, with a number of markers failing to yield positive values at any recombination fraction. Using multipoint H-LODS, the strongest evidence for linkage occurs under the narrow phenotypic definition and recessive genetic model, with a peak at marker DSS804 (max 3.35, P=0.0002). Multipoint nonparametric linkage analysis produced a peak in the same location (max z=2.84, P=0.002) with the narrow phenotypic definition. This putative vulnerability locus appears to be segregating in 10-25% of the families studied, but this estimate is tentative. Comparison of individual family multipoint H-LOD scores at the regions of interest on chromosomes 6p, 8p and 5q showed that only a minority of families yield high Iod scores in two or three regions. [ABSTRACT FROM AUTHOR]

Published
1997
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25. Examination of new and reported data of the DRD3/MscI polymorphism: no support for the proposed association with schizophrenia.

Author

Hawi, Z., McCabe, U., Straub, R.E., O'Neill, A., Kendler, K.S., Walsh, D., and Gill, M.

Subjects
DOPAMINE, RECEPTOR antibodies
Abstract

The dopamine D3 (DRD3) receptor gene has been implicated in the aetiology of schizophrenia as a candidate gene since it combines both the dopamine receptor and limbic hypotheses of the disease. Previous association studies of a DRD3/Mscl polymorphism suggested an increased frequency of homozygosity at the DRD3 receptor gene in schizophrenia. Homozygosity appeared to be particularly frequent in male patients, individuals with family history of the disease and in good responders to neuroleptic treatment. Many studies have since examined this polymorphism and have altered or extended the original homozygosity hypothesis. In this study, we have investigated the distribution of the DRD3/Mscl polymorphism in 198 Irish schizophrenic patients and 235 ethnically matched controls. Patients and controls showed similar allele and genotype frequencies. Furthermore, linkage analysis using two microsatellite markers flanking the DRD3 gene was performed on 265 Irish schizophrenic families, with substantially negative results. Our findings, in combination with a review of previous studies do not support a role for the DRD3/Mscl polymorphism in the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

Published
1998
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28. Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia

Author

Pardiñas, Antonio F., Smart, Sophie E., Corvin, Aiden, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Gershon, Elliot S., Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Fanous, Ayman H., Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, Haan, Lieuwe de, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Frank, Josef, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Kelly, Brian, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, McQuillin, Andrew, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Keong, Jimmy Lee Chee, Lee, S. Hong, Melle, Ingrid, Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Mortensen, Preben B., Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Mowry, Bryan J., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Pato, Carlos N., Morris, Derek W., Mors, Ole, Murphy, Kieran C., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Periyasamy, Sathish, Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O’Callaghan, Eadbhard, O’Dushlaine, Colm, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Os, Jim Van, Willcocks, Isabella R., Rietschel, Marcella, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietiläinen, Olli, Pimm, Jonathan, Rujescu, Dan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Simonsen, Carmen, Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., St Clair, David, Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Tooney, Paul, Spencer, Chris C. A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T. Scott, Subramaniam, Mythily, Wu, Jing Qin, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Söderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Andreassen, Ole A., Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H. M., Kowalec, Kaarina, Wormley, Brandon K., Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Blackwood, Douglas H. R., Sullivan, Patrick F., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Murray, Robin M., Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Holmans, Peter A., Owen, Michael J., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., Moran, Jennifer L., Nöthen, Markus M., Ophoff, Roel A., Palotie, Aarno, Petryshen, Tracey L., MacCabe, James H., Posthuma, Danielle, Riley, Brien P., Sham, Pak C., Sklar, Pamela, Clair, David St, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Agbedjro, Deborah, O’Donovan, Michael C., Stahl, Daniel, Kapur, Shitij, Millgate, Edward, Kepinska, Adrianna, Kravariti, Eugenia, Ajnakina, Olesya, Alameda, Luis, Barnes, Thomas R. E., Berardi, Domenico, Bonora, Elena, Walters, James T. R., Camporesi, Sara, Cleusix, Martine, Conus, Philippe, Crespo-Facorro, Benedicto, D’Andrea, Giuseppe, Demjaha, Arsime, Do, Kim Q., Doody, Gillian A., Eap, Chin B., Ferchiou, Aziz, Ripke, Stephan, Di Forti, Marta, Guidi, Lorenzo, Homman, Lina, Jenni, Raoul, Joyce, Eileen M., Kassoumeri, Laura, Khadimallah, Inès, Lastrina, Ornella, Muratori, Roberto, Noyan, Handan, Neale, Benjamin M., O’Neill, Francis A., Pignon, Baptiste, Restellini, Romeo, Richard, Jean-Romain, Schürhoff, Franck, Španiel, Filip, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Üçok, Alp, Farh, Kai-How, Vázquez-Bourgon, Javier, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Dennison, Charlotte A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A ., Lynham, Amy J., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Legge, Sophie E., Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberly D., Chan, Raymond C. K., Chen, Ronald Y. L., Chen, Eric Y. H., Cheng, Wei, Baune, Bernhard T., Cheung, Eric F. C., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Bigdeli, Tim B., Davis, Kenneth L., Degenhardt, Franziska, Favero, Jurgen Del, DeLisi, Lynn E., Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Cairns, Murray J., Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Farrell, Martilias S., Franke, Lude, Freedman, Robert, Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances (STRATA) Consortium and the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC), Ripke, S., Neale, B.M., Farh, K.H., Lee, P., Bulik-Sullivan, B., Collier, D.A., Huang, H., Pers, T.H., Agartz, I., Agerbo, E., Albus, M., Alexander, M., Amin, F., Bacanu, S.A., Begemann, M., Belliveau, R.A., Bene, J., Bergen, S.E., Bevilacqua, E., Black, D.W., Bruggeman, R., Buccola, N.G., Buckner, R.L., Byerley, W., Cahn, W., Cai, G., Campion, D., Cantor, R.M., Carr, V.J., Carrera, N., Catts, S.V., Chambert, K.D., Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W., Cheung, EFC, Chong, S.A., Cloninger, C.R., Cohen, D., Cohen, N., Cormican, P., Craddock, N., Crowley, J.J., Curtis, D., Davidson, M., Davis, K.L., Degenhardt, F., Favero, J.D., DeLisi, L.E., Demontis, D., Dikeos, D., Dinan, T., Djurovic, S., Donohoe, G., Drapeau, E., Duan, J., Dudbridge, F., Durmishi, N., Eichhammer, P., Eriksson, J., Escott-Price, V., Essioux, L., Farrell, M.S., Franke, L., Freedman, R., Freimer, N.B., Friedl, M., Friedman, J.I., Fromer, M., Genovese, G., Georgieva, L., Gershon, E.S., Giegling, I., Giusti-Rodríguez, P., Godard, S., Goldstein, J.I., Golimbet, V., Gopal, S., Gratten, J., Haan, L., Hammer, C., Hamshere, M.L., Hansen, M., Hansen, T., Haroutunian, V., Hartmann, A.M., Henskens, F.A., Herms, S., Hirschhorn, J.N., Hoffmann, P., Hofman, A., Hollegaard, M.V., Hougaard, D.M., Ikeda, M., Joa, I., Julià, A., Kahn, R.S., Kalaydjieva, L., Karachanak-Yankova, S., Karjalainen, J., Kavanagh, D., Keller, M.C., Kennedy, J.L., Khrunin, A., Kim, Y., Klovins, J., Knowles, J.A., Konte, B., Kucinskas, V., Kucinskiene, Z.A., Kuzelova-Ptackova, H., Kähler, A.K., Laurent, C., Keong, JLC, Lee, S.H., Lerer, B., Li, M., Li, T., Liang, K.Y., Lieberman, J., Limborska, S., Loughland, C.M., Lubinski, J., Lönnqvist, J., Macek, M., Magnusson, PKE, Maher, B.S., Maier, W., Mallet, J., Marsal, S., Mattheisen, M., Mattingsdal, M., McCarley, R.W., McDonald, C., McIntosh, A.M., Meier, S., Meijer, C.J., Melegh, B., Melle, I., Mesholam-Gately, R.I., Metspalu, A., Michie, P.T., Milani, L., Milanova, V., Mokrab, Y., Morris, D.W., Mors, O., Murphy, K.C., Myin-Germeys, I., Müller-Myhsok, B., Nelis, M., Nenadic, I., Nertney, D.A., Nestadt, G., Nicodemus, K.K., Nikitina-Zake, L., Nisenbaum, L., Nordin, A., O'Callaghan, E., O'Dushlaine, C., O'Neill, F.A., Oh, S.Y., Olincy, A., Olsen, L., Os, J.V., Pantelis, C., Papadimitriou, G.N., Papiol, S., Parkhomenko, E., Pato, M.T., Paunio, T., Pejovic-Milovancevic, M., Perkins, D.O., Pietiläinen, O., Pimm, J., Pocklington, A.J., Powell, J., Price, A., Pulver, A.E., Purcell, S.M., Quested, D., Rasmussen, H.B., Reichenberg, A., Reimers, M.A., Richards, A.L., Roffman, J.L., Roussos, P., Ruderfer, D.M., Salomaa, V., Sanders, A.R., Schall, U., Schubert, C.R., Schulze, T.G., Schwab, S.G., Scolnick, E.M., Scott, R.J., Seidman, L.J., Shi, J., Sigurdsson, E., Silagadze, T., Silverman, J.M., Sim, K., Slominsky, P., Smoller, J.W., So, H.C., Spencer, CCA, Stahl, E.A., Stefansson, H., Steinberg, S., Stogmann, E., Straub, R.E., Strengman, E., Strohmaier, J., Stroup, T.S., Subramaniam, M., Suvisaari, J., Svrakic, D.M., Szatkiewicz, J.P., Söderman, E., Thirumalai, S., Toncheva, D., Tosato, S., Veijola, J., Waddington, J., Walsh, D., Wang, D., Wang, Q., Webb, B.T., Weiser, M., Wildenauer, D.B., Williams, N.M., Williams, S., Witt, S.H., Wolen, A.R., Wong, EHM, Wormley, B.K., Xi, H.S., Zai, C.C., Zheng, X., Zimprich, F., Wray, N.R., Stefansson, K., Visscher, P.M., Adolfsson, R., Blackwood, DHR, Bramon, E., Buxbaum, J.D., Børglum, A.D., Cichon, S., Darvasi, A., Domenici, E., Ehrenreich, H., Esko, T., Gejman, P.V., Gill, M., Gurling, H., Hultman, C.M., Iwata, N., Jablensky, A.V., Jönsson, E.G., Kendler, K.S., Kirov, G., Knight, J., Lencz, T., Levinson, D.F., Li, Q.S., Liu, J., Malhotra, A.K., McCarroll, S.A., Moran, J.L., Mortensen, P.B., Nöthen, M.M., Ophoff, R.A., Palotie, A., Petryshen, T.L., Posthuma, D., Riley, B.P., Sham, P.C., Sklar, P., Clair, D.S., Weinberger, D.R., Wendland, J.R., Werge, T., Daly, M.J., Agbedjro, D., Stahl, D., Kapur, S., Millgate, E., Kepinska, A., Kravariti, E., Medical Research Council (UK), Cardiff University, Welsh Government, Health and Care Research Wales, European Commission, Academy of Medical Sciences (UK), Research Council of Norway, K. G. Jebsen Centres for Medical Research, National Institute for Health Research (UK), University College London, Government of Canada, University of Manitoba, Swedish Research Council, National Institute of Mental Health (US), Kings College London, Public Health Agency (Northern Ireland), The Psychiatry Research Trust, Maudsley Charity, Swiss National Science Foundation, Fondation Alamaya, Ministry of Health of the Czech Republic, Instituto de Salud Carlos III, Plan Nacional sobre Drogas (España), Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Wellcome Trust, and Universidad de Cantabria

Subjects
Male, endocrine system, Multifactorial Inheritance, animal structures, Psychiatry and Behavioral Health, Online First, Humans, Genetic Predisposition to Disease, ddc:610, Neurogenetics, Medicinsk genetik, Original Investigation, Research, Schizophrenia Sprectum and Other Psychotic Disorders, Featured, Genetics and genomics, Psychiatry and Mental health, Neurology, Psychotic Disorders, Schizophrenia, Female, Medical Genetics, hormones, hormone substitutes, and hormone antagonists, Comments, Genome-Wide Association Study
Abstract

[Importance] About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts., [Objective] To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples., [Design, Setting, and Participants] Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G])., [Main Outcomes and Measures] GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition., [Results] The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04)., [Conclusions and Relevance] In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance., This work was supported by Medical Research Council Centre grant MR/L010305/1, Medical Research Council Program grant MR/P005748/1, and Medical Research Council Project grants MR/L011794/1 and MC_PC_17212 to Cardiff University and by the National Centre for Mental Health, funded by the Welsh Government through Health and Care Research Wales. This work acknowledges the support of the Supercomputing Wales project, which is partially funded by the European Regional Development Fund via the Welsh Government. Dr Pardiñas was supported by an Academy of Medical Sciences Springboard Award (SBF005\1083). Dr Andreassen was supported by the Research Council of Norway (grants 283798, 262656, 248980, 273291, 248828, 248778, and 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, and the European Union’s Horizon 2020 Research and Innovation Programme (grant 847776). Dr Ajnakina was supported by an National Institute for Health Research postdoctoral fellowship (PDF-2018-11-ST2-020). Dr Joyce was supported by the University College London Hospitals/UCL University College London Biomedical Research Centre. Dr Kowalec received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (793530) from the government of Canada Banting postdoctoral fellowship programme and the University of Manitoba. Dr Sullivan was supported by the Swedish Research Council (Vetenskapsrådet, D0886501), the European Union’s Horizon 2020 programme (COSYN, 610307) and the US National Institute of Mental Health (U01 MH109528 and R01 MH077139). The Psychiatric Genomics Consortium was partly supported by the National Institute Of Mental Health (grants R01MH124873). The Sweden Schizophrenia Study was supported by the National Institute Of Mental Health (grant R01MH077139). The STRATA consortium was supported by a Stratified Medicine Programme grant to Dr MacCabe from the Medical Research Council (grant MR/L011794/1), which funded the research and supported Drs Pardiñas, Smart, Kassoumeri, Murray, Walters, and MacCabe. Dr Smart was supported by a Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital National Health Service Foundation Trust. The AESOP (US) cohort was funded by the UK Medical Research Council (grant G0500817). The Belfast (UK) cohort was funded by the Research and Development Office of Northern Ireland. The Bologna (Italy) cohort was funded by the European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Genetics and Psychosis project (London, UK) cohort was funded by the UK National Institute of Health Research Specialist Biomedical Research Centre for Mental Health, South London and the Maudsley National Health Service Mental Health Foundation Trust (SLAM) and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London; Psychiatry Research Trust; Maudsley Charity Research Fund; and the European Community’s Seventh Framework program (HEALTH-F2-2009-241909, project EU-GEI). The Lausanne (Switzerland) cohort was funded by the Swiss National Science Foundation (grants 320030_135736/1, 320030-120686, 324730-144064, 320030-173211, and 171804); the National Center of Competence in Research Synaptic Bases of Mental Diseases from the Swiss National Science Foundation (grant 51AU40_125759); and Fondation Alamaya. The Oslo (Norway) cohort was funded by the Research Council of Norway (grant 223273/F50, under the Centers of Excellence funding scheme, 300309, 283798) and the South-Eastern Norway Regional Health Authority (grants 2006233, 2006258, 2011085, 2014102, 2015088, and 2017-112). The Paris (France) cohort was funded by European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Prague (Czech Republic) cohort was funded by the Ministry of Health of the Czech Republic (grant NU20-04-00393). The Santander (Spain) cohort was funded by the following grants to Dr Crespo-Facorro: Instituto de Salud Carlos III (grants FIS00/3095, PI020499, PI050427, and PI060507), Plan Nacional de Drogas Research (grant 2005-Orden sco/3246/2004), SENY Fundatio Research (grant 2005-0308007), Fundacion Marques de Valdecilla (grant A/02/07, API07/011) and Ministry of Economy and Competitiveness and the European Fund for Regional Development (grants SAF2016-76046-R and SAF2013-46292-R). The West London (UK) cohort was funded by The Wellcome Trust (grants 042025, 052247, and 064607).

Published
2022

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