Common variant at 16p11.2 conferring risk of psychosis
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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 18 206 cases and 42 536 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 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 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 22 651 additional Icelanders).
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Schizophrenia appears to be associated more strongly with 16p11.2 duplications than with deletions.
“Schizophrenia (SZ) appears to be associated more strongly with 16p11.2 duplications [9, 25–27].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [25]
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Self-citationCandidate Gene–Environment Interaction Research
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Self-citationCognitive dysfunction in bipolar disorder and schizophrenia: a systematic review of meta-analyses
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Genetic Relationships Between Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder
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Copy number variation in bipolar disorder
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16p11.2 Copy Number Variations and Neurodevelopmental Disorders
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Kctd13 deletion reduces synaptic transmission via increased RhoA
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Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia
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Major Histocompatibility Complex I in Brain Development and Schizophrenia
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Self-citationVascular contributions to 16p11.2 deletion autism syndrome modeled in mice
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A Population-Based Study of Genetic Variation and Psychotic Experiences in Adolescents
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‘Big data’ in mental health research: current status and emerging possibilities
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Genomic and Epigenomic Insights into Nutrition and Brain Disorders
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Self-citationKctd13-deficient mice display short-term memory impairment and sex-dependent genetic interactions
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Maternal Modifiers and Parent-of-Origin Bias of the Autism-Associated 16p11.2 CNV
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Autism spectrum disorder, developmental and psychiatric features in 16p11.2 duplication
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Self-citationConvergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene
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Self-citationGWAS meta analysis identifies TSNARE1 as a novel Schizophrenia / Bipolar susceptibility locus
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Copy Number Variation Distribution in Six Monozygotic Twin Pairs Discordant for Schizophrenia
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Epilepsy and bipolar disorder.
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Self-citationHigh-Quality Exome Sequencing of Whole-Genome Amplified Neonatal Dried Blood Spot DNA
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Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders
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Rare and common variants at 16p11.2 are associated with schizophrenia
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Towards the clinical implementation of pharmacogenetics in bipolar disorder
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Risk genes for schizophrenia: Translational opportunities for drug discovery
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Self-citationNovel treatment strategies for schizophrenia from improved understanding of genetic risk
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Accumulation of minor alleles and risk prediction in schizophrenia
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Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis
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Self-citationConvergent functional genomics of psychiatric disorders
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Psychotic symptoms in 16p11.2 copy‐number variant carriers
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Self-citationThe pleiotropic spectrum of proximal 16p11.2 CNVs
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Haplotype-specific MAPK3 expression in 16p11.2 deletion contributes to variable neurodevelopment
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Dimensional Deconstruction and Reconstruction of CNV-Associated Neuropsychiatric Disorders
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Suche nach Risikogenen bei Schizophrenie
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The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation
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Neurobiologie der Schizophrenie
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Evaluation of whole genome amplified DNA to decrease material expenditure and increase quality
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Self-citationGWAS, Cytomegalovirus Infection, and Schizophrenia
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Self-citationCarbonyl stress in schizophrenia
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Effects of heterozygous deletion of autism-related gene Cullin-3 in mice
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Genome-wide association study of behavioural and psychiatric features in human prion disease
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TAOK2 controls synaptic plasticity and anxiety via ERK and calcium signaling
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Self-citationAutism risk gene Cul3 alters neuronal morphology via caspase-3 activity in mouse hippocampal neurons
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Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder
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An Entropy-Regularized Framework for Detecting Copy Number Variants
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Convolutional Neural Network Visualization for Identification of Risk Genes in Bipolar Disorder
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Genetic factors in the etiology of bipolar disorder
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Genetic factors in the etiology of bipolar disorder
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Self-citationFaculty Opinions recommendation of Copy number variation in bipolar disorder.
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Neurodevelopmental Mechanisms for Psychotic Disorders
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Role of cryptic rearrangements of human chromosomes in the aetiology of schizophrenia
Jurisova, L., & Šolc, R. (2023) · Journal of Genetics · doi:10.1007/s12041-023-01427-9
Hayes, C., Halverson, H. E., Keeran, K., Tison, K., Jacobo, K., Karki, A., Herring, I., Tunuguntla, S., Pace, M., Doan, B., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.20.565320
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Thompson, A. G. B. (2014) · UCL Discovery (University College London)
Bolat, H., Ünsel‐Bolat, G., Bulut, E., Özgül, S., Turan, D. S., Çelik, S., Koyuncu, Ö. O., Kırbıyık, Ö., Kaya, Ö. Ö., Kutbay, Y. B., et al. (2026) · Research in Autism · doi:10.1016/j.reia.2026.202865
- Authors
- Steinberg, S., de Jong, S., Mattheisen, M., Costas, J., Demontis, D., Jamain, S., Pietiläinen, 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., Lönnqvist, J., Paunio, T., Olsen, L., Hansen, T., Ingason, A., Pirinen, M., Strengman, E., GROUP, Hougaard, D. M., Ørntoft, T., Didriksen, M., Hollegaard, M. V., Nordentoft, M., Abramova, L., Kaleda, V, Arrojo, M., Sanjuán, J., Arango, C., Etain, B., Bellivier, F., Méary, A., Schürhoff, 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., Réthelyi, J. M., Bitter, I., Terenius, L., Jönsson, 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., Børglum, A. D., Mors, O., Mortensen, P. B., Werge, T., Ophoff, R. A., Nöthen, M. M., Rietschel, M., Cichon, S., Ruggeri, M., Tosato, S., Palotie, A., St Clair, D., Rujescu, D., Collier, D. A., Stefansson, H., & Stefansson, K.
- Affiliations
- deCODE Genetics (Iceland) (IS)
- Brigham and Women's Hospital (US)
- Complejo Hospitalario Universitario de Santiago (ES)
- Aarhus University (DK)
- Inserm (FR)
- University of Helsinki (FI)
- King's College London (GB)
- Max Planck Institute of Experimental Medicine (DE)
- Ludwig-Maximilians-Universität München (DE)
- Heidelberg University (DE)
- University of Aberdeen (GB)
- Oslo University Hospital (NO)
- University of Copenhagen (DK)
- Centre for Human Genetics (GB)
- University Medical Center Utrecht (NL)
- Statens Serum Institut (DK)
- Copenhagen University Hospital (DK)
- Mental Health Research Center of Russian Academy of Medical Sciences (RU)
- Universitat de València (ES)
- University of Rome Tor Vergata (IT)
- Radboud University Medical Center (NL)
- Radboud University Nijmegen (NL)
- Goethe University Frankfurt (DE)
- National University Hospital of Iceland (IS)
- Ss. Cyril and Methodius University in Skopje (MK)
- University of Belgrade (RS)
- Tbilisi State Medical University (GE)
- Ilia State University (GE)
- Centre for Addiction and Mental Health (CA)
- Black Dog Institute (AU)
- UNSW Sydney (AU)
- QIMR Berghofer Medical Research Institute (AU)
- Maastricht University Medical Centre (NL)
- Semmelweis University (HU)
- Karolinska Institutet (SE)
- Trinity College Dublin (IE)
- Queen's University Belfast (GB)
- Virginia Commonwealth University (US)
- Cardiff University (GB)
- Universidade de Santiago de Compostela (ES)
- University of California, Los Angeles (US)
- University of Bonn (DE)
- Forschungszentrum Jülich (DE)
- University of Verona (IT)
- Broad Institute (US)
- Eli Lilly (United Kingdom) (GB)
- ORCID
- Steinberg, S
- Mattheisen, M
- Costas, J
- Demontis, D
- Jamain, S
- Pietiläinen, O P H
- Papiol, S
- Vassos, E
- Giegling, I
- Melle, I
- Djurovic, S
- Agartz, I
- Suvisaari, J
- Lönnqvist, J
- Paunio, T
- Olsen, L
- Hansen, T
- Ingason, A
- Pirinen, M
- Strengman, E
- Hougaard, D M
- Didriksen, M
- Hollegaard, M V
- Nordentoft, M
- Arrojo, M
- Sanjuán, J
- Arango, C
- Bellivier, F
- Schürhoff, F
- Ribolsi, M
- Siracusano, A
- Rossner, M
- Christiansen, C
- Kiemeney, L A
- Franke, B
- Veldink, J
- Curran, S
- Bolton, P
- Poot, M
- Staal, W
- Kilpinen, H
- Freitag, C M
- Magnusson, P
- Martsenkovsky, I
- Martsenkovska, I
- Raleva, M
- Silagadze, T
- Mikeladze, N
- Vincent, J B
- Mitchell, P B
- Schofield, P R
- Fullerton, J M
- Montgomery, G W
- Martin, N G
- Rubino, I A
- Kenis, G
- Réthelyi, J M
- Bitter, I
- Terenius, L
- Jönsson, E G
- Jablensky, A
- Leboyer, M
- Bramon, E
- Powell, J
- Murray, R
- Corvin, A
- Gill, M
- Morris, D
- Kendler, K
- Riley, B
- Craddock, N
- Owen, M J
- Kong, A
- Ehrenreich, H
- Andreassen, O A
- Børglum, A D
- Mors, O
- Mortensen, P B
- Werge, T
- Ophoff, R A
- Nöthen, M M
- Rietschel, M
- Cichon, S
- Ruggeri, M
- Tosato, S
- Palotie, A
- Rujescu, D
- Collier, D A
- Venue
- Molecular Psychiatry
- Published
- 2012-11-20
- Volume
- 19
- Issue
- 1
- Pages
- 108-114
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3872086
- OpenAlex
- W2161749062
- Cited by
- 104
- References
- 76
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 12 · 2015: 16 · 2014: 20 · 2013: 10
- FWCI
- 10.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lirias (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- HAL (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- edoc (University of Basel) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- DZNE Pub (submittedVersion)
- GRO (submittedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, other-oa)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Autism Speaks
- Eli Lilly and Company
- Massachusetts General Hospital
- Strategiske Forskningsråd
- Helsingin Yliopisto
- Sundhed og Sygdom, Det Frie Forskningsråd
- Wellcome Trust (085475/Z/08/Z, 085475PELTONEN, 085475, 075491, 213506, 075491/Z/04,, 129680, 090532, 085475/B/08/Z, 098051, 076113)
- National Institute for Health and Care Research (NF-SI-0510-10268)
- British Heart Foundation (PG/13/66/30442)
- University of Oxford
- European Commission (213506, 242257, LSHM-CT-2006-037761, 218251, 223423)
- Academy of Finland (129680, #213506)
- Bundesministerium für Bildung und Forschung (01GS08147, 01GS08144)
- Max-Planck-Gesellschaft
- Vetenskapsrådet
- Norges Forskningsråd (#163070/V50)
- Universität des Saarlandes (T6 03 10 00‐45, T6 03 10 00)
- Centro de Investigación Biomédica en Red de Salud Mental
- Hersenstichting
- Xunta de Galicia
- H. Lundbeck A/S
- National Institutes of Health (n01mh80001-12-0-0)
- Medical Research Council (MR/L010305/1)
- National Institute of Mental Health (U24MH081810, MH074027, R01MH078075, MH900001, R01MH083094, MH078075, R01MH074027, 2N01MH080001-001, N01MH900001)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- psychosis, schizophrenia, bipolar disorder, 16p11.2, copy number variation, genetic risk, body mass index, genome-wide association study, Icelandic population
- MeSH terms
- Adult, Aged, Aged, 80 and over, Bipolar Disorder, Chromosome Aberrations, Chromosomes, Human, Pair 16, Europe, Female, Genotype, Humans, International Cooperation, Male, Middle Aged, Risk Factors, Schizophrenia, Odds Ratio, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Gene Expression Profiling, Genome-Wide Association Study, Young Adult
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