Search

Your search keyword '"Sundet, K."' showing total 320 results
Start Over Author "Sundet, K."
320 results on '"Sundet, K."'

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

Author

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

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Clinical Sciences, Psychology, Genetics, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

This corrects the article DOI: 10.1038/mp.2016.244.

Published
2017

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

Author

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

Subjects
Psychiatry, Medical and Health Sciences, Biological Sciences, Psychology and Cognitive Sciences
Abstract

This corrects the article DOI: 10.1038/mp.2016.244.

Published
2017

3. TCF4 sequence variants and mRNA levels are associated with neurodevelopmental characteristics in psychotic disorders.

Author

Wirgenes, KV, Sønderby, IE, Haukvik, UK, Mattingsdal, M, Tesli, M, Athanasiu, L, Sundet, K, Røssberg, JI, Dale, AM, Brown, AA, Agartz, I, Melle, I, Djurovic, S, and Andreassen, OA

Subjects
Brain, Humans, Transcription Factors, RNA, Messenger, Sequence Analysis, DNA, Affective Disorders, Psychotic, Psychotic Disorders, Schizophrenia, Neuropsychological Tests, Psychometrics, Schizophrenic Psychology, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Alleles, Adult, Middle Aged, Female, Male, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Genetic Variation, Transcription Factor 4, bipolar disorder, mRNA, neurodevelopment, psychotic phenotypes, schizophrenia, transcription factor 4, RNA, Messenger, Sequence Analysis, DNA, Affective Disorders, Psychotic, Polymorphism, Single Nucleotide, Psychology, Clinical Sciences, Public Health and Health Services
Abstract

TCF4 is involved in neurodevelopment, and intergenic and intronic variants in or close to the TCF4 gene have been associated with susceptibility to schizophrenia. However, the functional role of TCF4 at the level of gene expression and relationship to severity of core psychotic phenotypes are not known. TCF4 mRNA expression level in peripheral blood was determined in a large sample of patients with psychosis spectrum disorders (n = 596) and healthy controls (n = 385). The previously identified TCF4 risk variants (rs12966547 (G), rs9960767 (C), rs4309482 (A), rs2958182 (T) and rs17512836 (C)) were tested for association with characteristic psychosis phenotypes, including neurocognitive traits, psychotic symptoms and structural magnetic resonance imaging brain morphometric measures, using a linear regression model. Further, we explored the association of additional 59 single nucleotide polymorphisms (SNPs) covering the TCF4 gene to these phenotypes. The rs12966547 and rs4309482 risk variants were associated with poorer verbal fluency in the total sample. There were significant associations of other TCF4 SNPs with negative symptoms, verbal learning, executive functioning and age at onset in psychotic patients and brain abnormalities in total sample. The TCF4 mRNA expression level was significantly increased in psychosis patients compared with controls and positively correlated with positive- and negative-symptom levels. The increase in TCF4 mRNA expression level in psychosis patients and the association of TCF4 SNPs with core psychotic phenotypes across clinical, cognitive and brain morphological domains support that common TCF4 variants are involved in psychosis pathology, probably related to abnormal neurodevelopment.

Published
2012

4. Genome-wide autozygosity is associated with lower general cognitive ability

Author

Howrigan, D P, Simonson, M A, Davies, G, Harris, S E, Tenesa, A, Starr, J M, Liewald, D C, Deary, I J, McRae, A, Wright, M J, Montgomery, G W, Hansell, N, Martin, N G, Payton, A, Horan, M, Ollier, W E, Abdellaoui, A, Boomsma, D I, DeRosse, P, Knowles, E E M, Glahn, D C, Djurovic, S, Melle, I, Andreassen, O A, Christoforou, A, Steen, V M, Hellard, S L, Sundet, K, Reinvang, I, Espeseth, T, Lundervold, A J, Giegling, I, Konte, B, Hartmann, A M, Rujescu, D, Roussos, P, Giakoumaki, S, Burdick, K E, Bitsios, P, Donohoe, G, Corley, R P, Visscher, P M, Pendleton, N, Malhotra, A K, Neale, B M, Lencz, T, and Keller, M C

Published
2016
Full Text
View/download PDF

5. Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT)

Author

Lencz, T, Knowles, E, Davies, G, Guha, S, Liewald, D C, Starr, J M, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, Mukherjee, S, DeRosse, Pamela, Lundervold, A, Steen, V M, John, M, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, J G, Giegling, I, Konte, B, Ikeda, M, Roussos, P, Giakoumaki, S, Burdick, K E, Payton, A, Ollier, W, Horan, M, Donohoe, G, Morris, D, Corvin, A, Gill, M, Pendleton, N, Iwata, N, Darvasi, A, Bitsios, P, Rujescu, D, Lahti, J, Hellard, S L, Keller, M C, Andreassen, O A, Deary, I J, Glahn, D C, and Malhotra, A K

Published
2014
Full Text
View/download PDF

6. The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Author

Richards, AL, Pardinas, AF, Frizzati, A, Tansey, KE, Lynham, AJ, Holmans, P, Legge, SE, Savage, JE, Agartz, I, Andreassen, OA, Blokland, GAM, Corvin, A, Cosgrove, D, Degenhardt, F, Djurovic, S, Espeseth, T, Ferraro, L, Gayer-Anderson, C, Giegling, I, van Haren, Neeltje, Hartmann, AM, Hubert, JJ, Jönsson, EG, Konte, B, Lennertz, L, Olde Loohuis, LM, Melle, I, Morgan, C, Morris, DW, Murray, RM, Nyman, H, Ophoff, RA, Petryshen, TL, Quattrone, A, Rietschel, M, Rujescu, D, Rutten, B, Streit, F, Strohmeier, J, Sullivan, PF, Sundet, K, Wagner, M, Escott-Price, V, Owen, MJ, Donohoe, G, O'Donovan, MC, Walters, JTR, Richards, AL, Pardinas, AF, Frizzati, A, Tansey, KE, Lynham, AJ, Holmans, P, Legge, SE, Savage, JE, Agartz, I, Andreassen, OA, Blokland, GAM, Corvin, A, Cosgrove, D, Degenhardt, F, Djurovic, S, Espeseth, T, Ferraro, L, Gayer-Anderson, C, Giegling, I, van Haren, Neeltje, Hartmann, AM, Hubert, JJ, Jönsson, EG, Konte, B, Lennertz, L, Olde Loohuis, LM, Melle, I, Morgan, C, Morris, DW, Murray, RM, Nyman, H, Ophoff, RA, Petryshen, TL, Quattrone, A, Rietschel, M, Rujescu, D, Rutten, B, Streit, F, Strohmeier, J, Sullivan, PF, Sundet, K, Wagner, M, Escott-Price, V, Owen, MJ, Donohoe, G, O'Donovan, MC, and Walters, JTR

Published
2020

8. Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis

Author

Bourne, C., Aydemir, Ö., Balanzá-Martínez, V., Bora, E., Brissos, S., Cavanagh, J. T. O., Clark, L., Cubukcuoglu, Z., Dias, V. V., Dittmann, S., Ferrier, I. N., Fleck, D. E., Frangou, S., Gallagher, P., Jones, L., Kieseppä, T., Martínez-Aran, A., Melle, I., Moore, P. B., Mur, M., Pfennig, A., Raust, A., Senturk, V., Simonsen, C., Smith, D. J., Bio, D. S., Soeiro-de-Souza, M. G., Stoddart, S. D. R., Sundet, K., Szöke, A., Thompson, J. M., Torrent, C., Zalla, T., Craddock, N., Andreassen, O. A., Leboyer, M., Vieta, E., Bauer, M., Worhunsky, P. D., Tzagarakis, C., Rogers, R. D., Geddes, J. R., and Goodwin, G. M.

Published
2013
Full Text
View/download PDF

15. 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

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

Author

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

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

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

Published
2019

17. 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

18. 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

25. 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

26. 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

27. 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

28. 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

29. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Boehmer, AC, Boyle, PA, Brodaty, H, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kahonen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Knopman, DS, Kochan, NA, Konte, B, Kwok, JB, Le Hellard, S, Lee, T, Lehtimaki, T, Li, S-C, Liu, T, Koini, M, London, E, Longstreth, WT, Lopez, OL, Loukola, A, Luck, T, Lundervold, AJ, Lundquist, A, Lyytikainen, L-P, Martin, NG, Montgomery, GW, Murray, AD, Need, AC, Noordam, R, Nyberg, L, Ollier, W, Papenberg, G, Pattie, A, Polasek, O, Poldrack, RA, Psaty, BM, Reppermund, S, Riedel-Heller, SG, Rose, RJ, Rotter, JI, Roussos, P, Rovio, SP, Saba, Y, Sabb, FW, Sachdev, PS, Satizabal, CL, Schmid, M, Scott, RJ, Scult, MA, Simino, J, Slagboom, PE, Smyrnis, N, Soumare, A, Stefanis, NC, Stott, DJ, Straub, RE, Sundet, K, Taylor, AM, Taylor, KD, Tzoulaki, I, Tzourio, C, Uitterlinden, A, Vitart, V, Voineskos, AN, Kaprio, J, Wagner, M, Wagner, H, Weinhold, L, Wen, KH, Widen, E, Yang, Q, Zhao, W, Adams, HHH, Arking, DE, Bilder, RM, Bitsios, P, Boerwinkle, E, Chiba-Falek, O, Corvin, A, De Jager, PL, Debette, S, Donohoe, G, Elliott, P, Fitzpatrick, AL, Gill, M, Glahn, DC, Hagg, S, Hansell, NK, Hariri, AR, Ikram, MK, Jukema, JW, Vuoksimaa, E, Keller, MC, Kremen, WS, Launer, L, Lindenberger, U, Palotie, A, Pedersen, NL, Pendleton, N, Porteous, DJ, Raikkonen, K, Raitakari, OT, Ramirez, A, Reinvang, I, Rudan, I, Rujescu, D, Schmidt, R, Schmidt, H, Schofield, PW, Schofield, PR, Starr, JM, Steen, VM, Trollor, JN, Turner, ST, Van Duijn, CM, Villringer, A, Weinberger, DR, Weir, DR, Wilson, JF, Malhotra, A, McIntosh, AM, Gale, CR, Seshadri, S, Mosley, TH, Bressler, J, Lencz, T, Deary, IJ, Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Boehmer, AC, Boyle, PA, Brodaty, H, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kahonen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Knopman, DS, Kochan, NA, Konte, B, Kwok, JB, Le Hellard, S, Lee, T, Lehtimaki, T, Li, S-C, Liu, T, Koini, M, London, E, Longstreth, WT, Lopez, OL, Loukola, A, Luck, T, Lundervold, AJ, Lundquist, A, Lyytikainen, L-P, Martin, NG, Montgomery, GW, Murray, AD, Need, AC, Noordam, R, Nyberg, L, Ollier, W, Papenberg, G, Pattie, A, Polasek, O, Poldrack, RA, Psaty, BM, Reppermund, S, Riedel-Heller, SG, Rose, RJ, Rotter, JI, Roussos, P, Rovio, SP, Saba, Y, Sabb, FW, Sachdev, PS, Satizabal, CL, Schmid, M, Scott, RJ, Scult, MA, Simino, J, Slagboom, PE, Smyrnis, N, Soumare, A, Stefanis, NC, Stott, DJ, Straub, RE, Sundet, K, Taylor, AM, Taylor, KD, Tzoulaki, I, Tzourio, C, Uitterlinden, A, Vitart, V, Voineskos, AN, Kaprio, J, Wagner, M, Wagner, H, Weinhold, L, Wen, KH, Widen, E, Yang, Q, Zhao, W, Adams, HHH, Arking, DE, Bilder, RM, Bitsios, P, Boerwinkle, E, Chiba-Falek, O, Corvin, A, De Jager, PL, Debette, S, Donohoe, G, Elliott, P, Fitzpatrick, AL, Gill, M, Glahn, DC, Hagg, S, Hansell, NK, Hariri, AR, Ikram, MK, Jukema, JW, Vuoksimaa, E, Keller, MC, Kremen, WS, Launer, L, Lindenberger, U, Palotie, A, Pedersen, NL, Pendleton, N, Porteous, DJ, Raikkonen, K, Raitakari, OT, Ramirez, A, Reinvang, I, Rudan, I, Rujescu, D, Schmidt, R, Schmidt, H, Schofield, PW, Schofield, PR, Starr, JM, Steen, VM, Trollor, JN, Turner, ST, Van Duijn, CM, Villringer, A, Weinberger, DR, Weir, DR, Wilson, JF, Malhotra, A, McIntosh, AM, Gale, CR, Seshadri, S, Mosley, TH, Bressler, J, Lencz, T, and Deary, IJ

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

30. 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, Ida 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., 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, Ida 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., and 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.

Published
2018
Full Text
View/download PDF

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

Author

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

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

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

Author

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

Abstract

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

Published
2017

33. 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

34. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function

Author

University of Helsinki, Medicum, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, University of Helsinki, Helsinki Collegium for Advanced Studies, Trampush, J. W., Yang, M. L. Z., 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, Katri, Widen, E., Palotie, A., Eriksson, J. G., Giegling, I., Konte, B., Roussos, P., Giakoumaki, S., Burdick, K. E., Payton, A., Ollier, W., Horan, M., 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., University of Helsinki, Medicum, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, University of Helsinki, Helsinki Collegium for Advanced Studies, Trampush, J. W., Yang, M. L. Z., 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, Katri, Widen, E., Palotie, A., Eriksson, J. G., Giegling, I., Konte, B., Roussos, P., Giakoumaki, S., Burdick, K. E., Payton, A., Ollier, W., Horan, M., 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., and Lencz, T.

Abstract

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

Published
2017

35. Sex-dependent association of common variants of microcephaly genes with brain structure

Author

Rimol, L. M., Agartz, I., Djurovic, S., Brown, A. A., Roddey, J. C., Kahler, A. K., Mattingsdal, M., Athanasiu, L., Joyner, A. H., Schork, N. J., Halgren, E., Sundet, K., Melle, I., Dale, A. M., Andreassen, O. A., Weiner, M., Thal, L., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J., Toga, A. W., Beckett, L., Green, R. C., Gamst, A., Potter, W. Z., Montine, T., Anders, D., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Shaw, L., Lee, V. M.- Y., Korecka, M., Crawford, K., Neu, S., Harvey, D., Kornak, J., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Vorobik, R., Quinn, J., Schneider, L., Pawluczyk, S., Spann, B., Fleisher, A. S., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Yaakov, Honig, L. S., Bell, K. L., Morris, J. C., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Badger, B., Grossman, H., Tang, C., Stern, J., deToledo-Morrell, L., Shah, R. C., Bach, J., Duara, R., Isaacson, R., Strauman, S., Albert, M. S., Pedroso, J., Toroney, J., Rusinek, H., de Leon, M. J., De Santi, S. M., Doraiswamy, P. M., Petrella, J. R., Aiello, M., Clark, C. M., Pham, C., Nunez, J., Smith, C. D., Given II, C. A., Hardy, P., DeKosky, S. T., Oakley, M., Simpson, D. M., Ismail, M. S., Porsteinsson, A., McCallum, C., Cramer, S. C., Mulnard, R. A., McAdams-Ortiz, C., Diaz-Arrastia, R., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Laubinger, M. M., Bartzokis, G., Silverman, D. H. S., Lu, P. H., Fletcher, R., Parfitt, F., Johnson, H., Farlow, M., Herring, S., Hake, A. M., van Dyck, C. H., MacAvoy, M. G., Bifano, L. A., Chertkow, H., Bergman, H., Hosein, C., Black, S., Graham, S., Caldwell, C., Feldman, H., Assaly, M., Hsiung, G.-Y. R., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Gitelman, D., Johnson, N., Mesulam, M., Sadowsky, C., Villena, T., Mesner, S., Aisen, P. S., Johnson, K. B., Behan, K. E., Sperling, R. A., Rentz, D. M., Johnson, K. A., Rosen, A., Tinklenberg, J., Ashford, W., Sabbagh, M., Connor, D., Obradov, S., Killiany, R., Norbash, A., Obisesan, T. O., Jayam-Trouth, A., Wang, P., Auchus, A. P., Huang, J., Friedland, R. P., DeCarli, C., Fletcher, E., Carmichael, O., Kittur, S., Mirje, S., Johnson, S. C., Borrie, M., Lee, T.-Y., Asthana, S., Carlsson, C. M., Potkin, S. G., Highum, D., Preda, A., Nguyen, D., Tariot, P. N., Hendin, B. A., Scharre, D. W., Kataki, M., Beversdorf, D. Q., Zimmerman, E. A., Celmins, D., Brown, A. D., Gandy, S., Marenberg, M. E., Rovner, B. W., Pearlson, G., Blank, K., Anderson, K., Saykin, A. J., Santulli, R. B., Pare, N., Williamson, J. D., Sink, K. M., Potter, H., Ashok Raj, B., Giordano, A., Ott, B. R., Wu, C.-K., Cohen, R., Wilks, K. L., and Alzheimer's Disease Neuroimaging Initiative

Subjects
Adult, Male, Microcephaly, Molecular Sequence Data, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Brain mapping, ASPM, Sex Factors, medicine, Animals, Humans, SNP, Genetic Predisposition to Disease, Genetics, Brain Mapping, Multidisciplinary, CDK5RAP2, Brain morphometry, Brain, Middle Aged, Biological Sciences, medicine.disease, Magnetic Resonance Imaging, Phenotype, Brain size, Female
Abstract

Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717–728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637–644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2 , MCPH1 , and ASPM , with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample ( n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample ( n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.

Published
2009

37. Genome-wide autozygosity is associated with lower general cognitive ability

Author

Howrigan, D P, primary, Simonson, M A, additional, Davies, G, additional, Harris, S E, additional, Tenesa, A, additional, Starr, J M, additional, Liewald, D C, additional, Deary, I J, additional, McRae, A, additional, Wright, M J, additional, Montgomery, G W, additional, Hansell, N, additional, Martin, N G, additional, Payton, A, additional, Horan, M, additional, Ollier, W E, additional, Abdellaoui, A, additional, Boomsma, D I, additional, DeRosse, P, additional, Knowles, E E M, additional, Glahn, D C, additional, Djurovic, S, additional, Melle, I, additional, Andreassen, O A, additional, Christoforou, A, additional, Steen, V M, additional, Hellard, S L, additional, Sundet, K, additional, Reinvang, I, additional, Espeseth, T, additional, Lundervold, A J, additional, Giegling, I, additional, Konte, B, additional, Hartmann, A M, additional, Rujescu, D, additional, Roussos, P, additional, Giakoumaki, S, additional, Burdick, K E, additional, Bitsios, P, additional, Donohoe, G, additional, Corley, R P, additional, Visscher, P M, additional, Pendleton, N, additional, Malhotra, A K, additional, Neale, B M, additional, Lencz, T, additional, and Keller, M C, additional

Published
2015
Full Text
View/download PDF

38. Modelling difficulties in abstract thinking in psychosis: the importance of socio-developmental background.

Author

Berg, A. O., Melle, I., Zuber, V., Simonsen, C., Nerhus, M., Ueland, T., Andreassen, O. A., Sundet, K., and Vaskinn, A.

Subjects
PSYCHOSES, PSYCHIATRIC treatment, ABSTRACT thought, PSYCHOTIC depression, INTELLIGENCE levels, SCANDINAVIAN languages, IMMIGRANTS, MENTAL health, THERAPEUTICS
Abstract

Introduction:Abstract thinking is important in modern understanding of neurocognitive abilities, and a symptom of thought disorder in psychosis. In patients with psychosis, we assessed if socio-developmental background influences abstract thinking, and the association with executive functioning and clinical psychosis symptoms. Methods:Participants (n = 174) had a diagnosis of psychotic or bipolar disorder, were 17–65 years, intelligence quotient (IQ) > 70, fluent in a Scandinavian language, and their full primary education in Norway. Immigrants (N = 58) were matched (1:2) with participants without a history of migration (N = 116). All participants completed a neurocognitive and clinical assessment. Socio-developmental background was operationalised as human developmental index (HDI) of country of birth, at year of birth. Structural equation modelling was used to assess the model with best fit. Results:The model with best fit,χ2 = 96.591, df = 33,p < .001, confirmed a significant indirect effect of HDI scores on abstract thinking through executive functioning, but not through clinical psychosis symptoms. Conclusions:This study found that socio-developmental background influences abstract thinking in psychosis by indirect effect through executive functioning. We should take into account socio-developmental background in the interpretation of neurocognitive performance in patients with psychosis, and prioritise cognitive remediation in treatment of immigrant patients. [ABSTRACT FROM PUBLISHER]

Published
2017
Full Text
View/download PDF

39. Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT)

Author

Lencz, T, primary, Knowles, E, additional, Davies, G, additional, Guha, S, additional, Liewald, D C, additional, Starr, J M, additional, Djurovic, S, additional, Melle, I, additional, Sundet, K, additional, Christoforou, A, additional, Reinvang, I, additional, Mukherjee, S, additional, DeRosse, Pamela, additional, Lundervold, A, additional, Steen, V M, additional, John, M, additional, Espeseth, T, additional, Räikkönen, K, additional, Widen, E, additional, Palotie, A, additional, Eriksson, J G, additional, Giegling, I, additional, Konte, B, additional, Ikeda, M, additional, Roussos, P, additional, Giakoumaki, S, additional, Burdick, K E, additional, Payton, A, additional, Ollier, W, additional, Horan, M, additional, Donohoe, G, additional, Morris, D, additional, Corvin, A, additional, Gill, M, additional, Pendleton, N, additional, Iwata, N, additional, Darvasi, A, additional, Bitsios, P, additional, Rujescu, D, additional, Lahti, J, additional, Hellard, S L, additional, Keller, M C, additional, Andreassen, O A, additional, Deary, I J, additional, Glahn, D C, additional, and Malhotra, A K, additional

Published
2013
Full Text
View/download PDF

40. X linked mental retardation and infantile spasms in a family: new clinical data and linkage to Xp11.4-Xp22.11

Author

Strømme P, Sundet K, Mørk C, Jj, Cassiman, Jp, Fryns, and Stephan Claes

Subjects
Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, X Chromosome, Adolescent, Genetic Linkage, Original Articles, Middle Aged, Pedigree, Intellectual Disability, Humans, Lod Score, Spasms, Infantile, Aged, Spinocerebellar Degenerations
Abstract

In order to describe the neurological abnormalities and to identify the gene localisation, we re-evaluated a previously reported family with X linked mental retardation (XLMR). Reliable data were obtained for six of the seven affected males, of whom two had had infantile spasms. Profound MR (IQ

Published
1999

50. Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group

Author

Simonsen, C., primary, Sundet, K., additional, Vaskinn, A., additional, Birkenaes, A. B., additional, Engh, J. A., additional, Faerden, A., additional, Jonsdottir, H., additional, Ringen, P. A., additional, Opjordsmoen, S., additional, Melle, I., additional, Friis, S., additional, and Andreassen, O. A., additional

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results