Common variants at VRK2 and TCF4 conferring risk of schizophrenia

Date Issued
2011
Author(s)
Steinberg, Stacy
de Jong, Simone
Andreassen, Ole A.
Werge, Thomas
Børglum, Anders D.
Mors, Ole
Mortensen, Preben B.
Gustafsson, Omar
Costas, Javier
Pietiläinen, Olli P. H.
Demontis, Ditte
Huttenlocher, Johanna
Mattheisen, Manuel
Breuer, René
Vassos, Evangelos
Giegling, Ina
Fraser, Gillian
Walker, Nicholas
Tuulio-Henriksson, Annamari
Suvisaari, Jaana
Lönnqvist, Jouko
Paunio, Tiina
Agartz, Ingrid
Melle, Ingrid
Djurovic, Srdjan
Strengman, Eric
Jürgens, Gesche
Glenthøj, Birte
Terenius, Lars
Hougaard, David M.
Ørntoft, Torben
Wiuf, Carsten
Didriksen, Michael
Hollegaard, Mads V.
Nordentoft, Merete
Winkel, Ruud van
Kenis, Gunter
Abramova, Lilia
Kaleda, Vasily
Arrojo, Manuel
Sanjuán, Julio
Arango, Celso
Ribolsi, Michele
Magni, Valentina
Siracusano, Alberto
Christiansen, Claus
Kiemeney, Lambertus A.
Veldink, Jan
Van den Berg, Leonard
Ingason, Andres
Muglia, Pierandrea
Murray, Robin M.
Nöthen, Markus M.
Sigurdsson, Engilbert
Petursson, Hannes
Thorsteinsdottir, Unnur
Kong, Augustine
Rubino, I. Alex
Hert, Marc de
Réthelyi, János M.
Bitter, István
Jönsson, Erik G.
Golimbet, Vera
Carracedo, Angel
Craddock, Nick
Owen, Michael J.
O’Donovan, Michael C.
Ruggeri, Mirella
Tosato, Sarah
Peltonen, Leena
Ophoff, Roel A.
Collier, David A.
St Clair, David
Rietschel, Marcella
Cichon, Sven
Stefansson, Hreinn
Rujescu, Dan
Stefansson, Kari
DOI
10.1093/hmg/ddr325
Abstract
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)).