Truncating mutations in RBM12 are associated with psychosis
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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From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as Steinberg et al., 2017
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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)
- ORCID
- 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
- Licence
- 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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