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Common variants at VRK2 and TCF4 conferring risk of schizophrenia

Steinberg, S., de Jong, S., Andreassen, O. A., Werge, T., Borglum, A. D., Mors, O., Mortensen, P. B., Gustafsson, O., Costas, J., Pietilainen, O. P. H., Demontis, D., Papiol, S., Huttenlocher, J., Mattheisen, M., Breuer, R., Vassos, E., Giegling, I., Fraser, G., Walker, N., Tuulio-Henriksson, A., Suvisaari, J., Lonnqvist, J., Paunio, T., Agartz, I., Melle, I., Djurovic, S., Strengman, E., Jurgens, G., Glenthoj, B., Terenius, L., Hougaard, D, Orntoft, T., Wiuf, C., Didriksen, M., Hollegaard, M. V., Nordentoft, M., van Winkel, R., Kenis, G., Abramova, L., Kaleda, V., Arrojo, M., Sanjuan, J., Arango, C., Sperling, S., Rossner, M., Ribolsi, M., Magni, V., Siracusano, A., Christiansen, C., Kiemeney, L. A., Veldink, J., van den Berg, L., Ingason, A., Muglia, P., Murray, R., Nothen, M. M., Sigurdsson, E., Petursson, H., Thorsteinsdottir, U., Kong, A., Rubino, I. A., De Hert, M., Rethelyi, J. M., Bitter, I., Jonsson, E. G., Golimbet, V., Carracedo, A., Ehrenreich, H., Craddock, Nicholas John, Owen, Michael John, O'Donovan, Michael Conlon, Ruggeri, M., Tosato, S., Peltonen, L., Ophoff, R. A., Collier, D. A., St Clair, D., Rietschel, M., Cichon, S., Stefansson, H., Rujescu, D. and Stefansson, K. 2011. Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human Molecular Genetics 20 (20) , pp. 4076-4081. 10.1093/hmg/ddr325

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Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10−9] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10−9).

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Oxford University Press
ISSN: 0964-6906
Last Modified: 04 Jun 2017 03:46

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