Expanding the range of ZNF804A variants conferring risk of psychosis.
paper
Cited
Public
- Authors
- Steinberg, S; Mors, O; BΓΈrglum, A D; Gustafsson, O; Werge, T; Mortensen, P B; Andreassen, O A; Sigurdsson, E; Thorgeirsson, T E; BΓΆttcher, Y; Olason, P; Ophoff, R A; Cichon, S; Gudjonsdottir, I H; PietilΓ€inen, O P H; Nyegaard, M; Tuulio-Henriksson, A; Ingason, A; Hansen, T; Athanasiu, L; Suvisaari, J; Lonnqvist, J; Paunio, T; Hartmann, A; JΓΌrgens, G; Nordentoft, M; Hougaard, D; Norgaard-Pedersen, B; Breuer, R; MΓΆller, H-J; Giegling, I; GlenthΓΈj, B; Rasmussen, H B; Mattheisen, M; Bitter, I; RΓ©thelyi, J M; Sigmundsson, T; Fossdal, R; Thorsteinsdottir, U; Ruggeri, M; Tosato, S; Strengman, E; Genetic Risk and Outcome in Psychosis; Kiemeney, L A; Melle, I; Djurovic, S; Abramova, L; Kaleda, V; Walshe, M; Bramon, E; Vassos, E; Li, T; Fraser, G; Walker, N; Toulopoulou, T; Yoon, J; Freimer, N B; Cantor, R M; Murray, R; Kong, A; Golimbet, V; JΓΆnsson, E G; Terenius, L; Agartz, I; Petursson, H; NΓΆthen, M M; Rietschel, M; Peltonen, L; Rujescu, D; Collier, D A; Stefansson, H; St Clair, D; Stefansson, K
- Year
- 2011
- Journal
- Molecular psychiatry
- PMID
- 20048749
- DOI
- 10.1038/mp.2009.149
- PMCID
- PMC3242031
A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 Γ 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 Γ 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 Γ 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).
Large structural variants in ZNF804A.(a) A deletion in an Icelandic anxiety patient (patient 3), (b) a duplication in an Icelandic bipolar patient (patient 2), (c) a deletion in a Scottish schizophrenia patient (patient 1). The coordinates are based on NCBI Build 36.
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| Name | Type |
|---|---|
| 12,000 controls local | cohort |
| Aberdeen samples local | cohort |
| Affymetrix 6.0 chip local | drug |
| Affymetrix chip local | drug |
| African American | cohort |
| African-American parentβoffspring pair local | cohort |
| animal models | cohort |
| anxiety | phenotype |
| anxiety patients local | cohort |
| autism | phenotype |
| autism families local | cohort |
| Autism families local | cohort |
| bipolar disorder | phenotype |
| bipolar disorder patients local | cohort |
| Bonn cohort local | cohort |
| cases | cohort |
| Centaurus assays local | drug |
| CFTR | gene |
| Chinese | cohort |
| chr2:185,171,338-185,512,459 Mb NCBI Build 36 local | variant |
| CNTNAP2 | gene |
| CNV | variant |
| CNV_chr2_185171338_185512459 local | variant |
| combined follow-up sets local | cohort |
| Combined psychiatric disorders local | phenotype |
| combined sample | cohort |
| common PNPLA3 susceptibility allele local | variant |
| common variants | cohort |
| controls | cohort |
| control subjects | cohort |
| copy number variation | variant |
| cystic fibrosis | phenotype |
| Database of Genomic Variants local | cohort |
| deletion | variant |
| Denmark/Aarhus local | cohort |
| Denmark cohort | cohort |
| Denmark/Copenhagen local | cohort |
| depression | phenotype |
| depression patients local | cohort |
| duplication | variant |
| England | cohort |
| England cohort local | cohort |
| epilepsy | phenotype |
| European-American child local | cohort |
| European ancestry | cohort |
| Finland | cohort |
| Finland/excluding Kuusamo local | cohort |
| Finland (excluding Kuusamo) cohort local | cohort |
| Finland/Kuusamo local | cohort |
| Finland Kuusamo cohort local | cohort |
| Follow-up Chinese cohort local | cohort |
| follow-up data set local | cohort |
| Follow-up European cohort local | cohort |
| follow-up set 2 local | cohort |
| GC content local | drug |
| genome-wide typed samples local | cohort |
| Germany/Bonn local | cohort |
| Germany/Munich local | cohort |
| haploinsufficiency disorders local | phenotype |
| HapMap3 | cohort |
| HapMap CEU | cohort |
| HapMap CHB/JPT local | cohort |
| hepatic fat levels local | phenotype |
| hidden Markov model | drug |
| HumanHap300 | drug |
| Human-Hap300-duo local | drug |
| HumanHap550 | drug |
| HumanHap610 local | drug |
| Hungary | cohort |
| ICCSS | cohort |
| Iceland | cohort |
| Iceland cohort local | cohort |
| Illumina BeadStudio local | drug |
| Illumina chip local | drug |
| Illumina genome-wide typed local | cohort |
| Illumina genome-wide typed set local | cohort |
| Illumina HumanHap300 | drug |
| Illumina HumanHap550 local | drug |
| initial data set local | cohort |
| Initial European cohort local | cohort |
| International schizophrenia Consortium | cohort |
| ISC data set local | cohort |
| ISC dataset1 local | cohort |
| Italy | cohort |
| Italy cohort local | cohort |
| large CNVs | variant |
| MGS | anatomy |
| Molecular Genetics of Schizophrenia consortium local | cohort |
| mood disorders | phenotype |
| Munich cohort local | cohort |
| Netherlands | cohort |
| Netherlands cohort local | cohort |
| nonalcoholic fatty liver disease local | phenotype |
| Norway | cohort |
| Norwegian sample local | cohort |
| other psychiatric disorder patients local | cohort |
| other psychiatric disorders patients local | cohort |
| pathogenic CNVs local | variant |
| PennCNV | gene |
| PNPLA3 local | gene |
| PNPLA3 null sequence mutations local | variant |
| PNPLA3 protective allele local | variant |
| primary GWA study local | cohort |
| psychiatric disorders | phenotype |
| psychosis | phenotype |
| psychosis patients local | cohort |
| psychosis phenotype local | phenotype |
| psychosis-related phenotype local | phenotype |
| rare CNVs | variant |
| rare copy number variants | variant |
| rare variant | cohort |
| remaining groups local | cohort |
| rs12477914 local | variant |
| rs1344706 | variant |
| rs1366840 local | variant |
| Russia | cohort |
| schizophrenia | phenotype |
| Scotland | cohort |
| Scotland cohort local | cohort |
| single-marker typed samples local | cohort |
| SNP | cohort |
| STRUCTURE10 local | drug |
| Sweden | cohort |
| TCF2 local | gene |
| unrelated autism cases local | cohort |
| Unrelated autism cases local | cohort |
| ZNF804A | gene |
| ZNF804A 3' exons deletion local | variant |
| ZNF804A CNV local | variant |
| ZNF804A CNVs local | variant |
| ZNF804A copy number variation local | variant |
| ZNF804A deletion local | variant |
| ZNF804A duplication local | variant |
| ZNF804A full-gene deletion local | variant |
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