Common variant at 16p11.2 conferring risk of psychosis.
- Authors
- Steinberg, S; de Jong, S; Mattheisen, M; Costas, J; Demontis, D; Jamain, S; PietilΓ€inen, O P H; Lin, K; Papiol, S; Huttenlocher, J; Sigurdsson, E; Vassos, E; Giegling, I; Breuer, R; Fraser, G; Walker, N; Melle, I; Djurovic, S; Agartz, I; Tuulio-Henriksson, A; Suvisaari, J; LΓΆnnqvist, J; Paunio, T; Olsen, L; Hansen, T; Ingason, A; Pirinen, M; Strengman, E; GROUP; Hougaard, D M; Orntoft, T; Didriksen, M; Hollegaard, M V; Nordentoft, M; Abramova, L; Kaleda, V; Arrojo, M; SanjuΓ‘n, J; Arango, C; Etain, B; Bellivier, F; MΓ©ary, A; SchΓΌrhoff, F; Szoke, A; Ribolsi, M; Magni, V; Siracusano, A; Sperling, S; Rossner, M; Christiansen, C; Kiemeney, L A; Franke, B; van den Berg, L H; Veldink, J; Curran, S; Bolton, P; Poot, M; Staal, W; Rehnstrom, K; Kilpinen, H; Freitag, C M; Meyer, J; Magnusson, P; Saemundsen, E; Martsenkovsky, I; Bikshaieva, I; Martsenkovska, I; Vashchenko, O; Raleva, M; Paketchieva, K; Stefanovski, B; Durmishi, N; Pejovic Milovancevic, M; Lecic Tosevski, D; Silagadze, T; Naneishvili, N; Mikeladze, N; Surguladze, S; Vincent, J B; Farmer, A; Mitchell, P B; Wright, A; Schofield, P R; Fullerton, J M; Montgomery, G W; Martin, N G; Rubino, I A; van Winkel, R; Kenis, G; De Hert, M; RΓ©thelyi, J M; Bitter, I; Terenius, L; JΓΆnsson, E G; Bakker, S; van Os, J; Jablensky, A; Leboyer, M; Bramon, E; Powell, J; Murray, R; Corvin, A; Gill, M; Morris, D; O'Neill, F A; Kendler, K; Riley, B; Wellcome Trust Case Control Consortium 2; Craddock, N; Owen, M J; O'Donovan, M C; Thorsteinsdottir, U; Kong, A; Ehrenreich, H; Carracedo, A; Golimbet, V; Andreassen, O A; BΓΈrglum, A D; Mors, O; Mortensen, P B; Werge, T; Ophoff, R A; NΓΆthen, M M; Rietschel, M; Cichon, S; Ruggeri, M; Tosato, S; Palotie, A; St Clair, D; Rujescu, D; Collier, D A; Stefansson, H; Stefansson, K
- Year
- 2014
- Journal
- Molecular psychiatry
- PMID
- 23164818
- DOI
- 10.1038/mp.2012.157
- PMCID
- PMC3872086
Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18β206 cases and 42β536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46β160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 Γ 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22β651 additional Icelanders).
Association results and structure of the 16p11.2 region. Bars on the x-axis indicate segmental duplications (brown) and recombination hotspots (pink). Association results are illustrated for SGENE-plus (black), SGENE-plus+MGS+ISC (green), SGENE-plus+MGS+ISC plus the primary psychosis follow-up (blue), and SGENE-plus+MGS+ISC plus the primary psychosis and secondary schizophrenia follow-up (red). RefSeq genes in the region are shown below the plot.
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| 20 | Discussion | In conclusion, in this work, we broadened our phenotype of interest to psychosis, identifying a new⦠|
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