Cited by 104Schizophrenia research and treatmentGenetic Associations and EpidemiologyGenomic variations and chromosomal abnormalities

Common variant at 16p11.2 conferring risk of psychosis

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Steinberg, S, de Jong, S, Mattheisen, M, Costas, J, Demontis, D, Jamain, S, Pietiläinen, O P H, Lin, K +125 more·2014·Molecular Psychiatry

Abstract

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].”

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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)
Venue
Molecular Psychiatry
Published
2012-11-20
Volume
19
Issue
1
Pages
108-114
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
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
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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