Cited by 70Schizophrenia research and treatmentGenetic Associations and EpidemiologyGenomics and Rare Diseases

Truncating mutations in RBM12 are associated with psychosis

Steinberg, Stacy, Gudmundsdottir, Steinunn, Sveinbjornsson, Gardar, Suvisaari, Jaana, Paunio, Tiina, Torniainen-Holm, Minna, Frigge, Michael L, Jonsdottir, Gudrun A +12 more·2017·Nature Genetics

Abstract

Thus far, a handful of highly penetrant mutations conferring risk of psychosis have been discovered. Here we used whole-genome sequencing and long-range phasing to investigate an Icelandic kindred containing ten individuals with psychosis (schizophrenia, schizoaffective disorder or psychotic bipolar disorder). We found that all affected individuals carry RBM12 (RNA-binding-motif protein 12) c.2377G>T (P = 2.2 × 10-4), a nonsense mutation that results in the production of a truncated protein lacking a predicted RNA-recognition motif. We replicated the association in a Finnish family in which a second RBM12 truncating mutation (c.2532delT) segregates with psychosis (P = 0.020). c.2377G>T is not fully penetrant for psychosis; however, we found that carriers unaffected by psychosis resemble patients with schizophrenia in their non-psychotic psychiatric disorder and neuropsychological test profile (P = 0.0043) as well as in their life outcomes (including an increased chance of receiving disability benefits, P = 0.011). As RBM12 has not previously been linked to psychosis, this work provides new insight into psychiatric disease.

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Crossref · 10.1038/ng.3894

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Authors
Steinberg, S., Gudmundsdottir, S., Sveinbjornsson, G., Suvisaari, J., Paunio, T., Torniainen-Holm, M., Frigge, M. L., Jonsdottir, G. A., Huttenlocher, J., Arnarsdottir, S., Ingimarsson, O., Haraldsson, M., Tyrfingsson, T., Thorgeirsson, T. E., Kong, A., Norddahl, G. L., Gudbjartsson, D. F., Sigurdsson, E., Stefansson, H., & Stefansson, K.
Affiliations
  • deCODE Genetics (Iceland) (IS)
  • Finnish Institute for Health and Welfare (FI)
  • University of Helsinki (FI)
  • University of Iceland (IS)
Venue
Nature Genetics
Published
2017-06-19
Volume
49
Issue
8
Pages
1251-1254
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2626815279
Cited by
70
References
51
Citations by year
2025: 4 · 2024: 3 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 14 · 2018: 14 · 2017: 2
FWCI
8.58
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
Funders
  • Medical Research Council (MC_PC_15018)
  • National Institute on Drug Abuse (R01DA034076)
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 › Genomics and Rare Diseases
Keywords
psychosis, schizophrenia, nonsense mutation, frameshift mutation, truncating mutations, RNA-binding motif protein, genetic susceptibility, Finnish families, penetrance, neuropsychological profile, disability benefits, mental illness
MeSH terms
Family Health, Female, Humans, Iceland, Male, Psychotic Disorders, Genome, Human, RNA-Binding Proteins, Sequence Analysis, DNA, Codon, Nonsense

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