The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study
Abstract
OBJECTIVES: Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question. METHODS: We compared a national sample of individuals with Darier disease and their first-degree relatives with matched unexposed individuals from the general population and their first-degree relatives, respectively. To examine risks for bipolar disorder and schizophrenia, risk ratios and 95% confidence intervals (CIs) were estimated using conditional logistic regressions. RESULTS: Individuals with Darier disease had a 4.3 times higher risk of being diagnosed with bipolar disorder (95% CI: 2.6-7.3) and a 2.3 times higher risk of being diagnosed with schizophrenia (95% CI: 1.1-5.2) than matched individuals from the general population. Relatives of individuals with Darier disease had a 1.6 times higher risk of having bipolar disorder (95% CI: 1.1-2.5) than relatives of matched individuals from the general population, but no increased risk of schizophrenia (risk ratio = 0.8, 95% CI: 0.4-1.8). CONCLUSIONS: The association between Darier disease and bipolar disorder is manifest also in the population, and our data suggest that genetic variability within the ATP2A2 gene that causes Darier disease also confers susceptibility for bipolar disorder. The Darier-causing mutations merit additional attention in molecular genetic research on bipolar disorder.
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Mutations in ATP2A2 cause Darier Disease, which co-segregates with bipolar disorder in several multiplex pedigrees and is associated with bipolar disorder and schizophrenia at a population level.
“Mutations in ATP2A2 cause Darier Disease21, which co-segregates with bipolar disorder in several multiplex pedigrees and is associated with bipolar disorder and schizophrenia at a population level22.”
From Mapping genomic loci implicates genes and synaptic biology in schizophrenia (2022) · cites this paper as [22]
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Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Trubetskoy, V., Pardiñas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., Bryois, J., Chen, C.-Y., Dennison, C. A., Hall, L. S., et al. (2022) · Nature · doi:10.1038/s41586-022-04434-5 · Cited by 2,964 · see citing works
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- Authors
- Cederlöf, M., Bergen, S. E., Långström, N., Larsson, H., Boman, M., Craddock, N., Östberg, P., Lundström, S., Sjölander, A., Nordlind, K., Landén, M., & Lichtenstein, P.
- Affiliations
- Karolinska Institutet (SE)
- Swedish Prison and Probation Service (SE)
- Cardiff University (GB)
- Karolinska University Hospital (SE)
- University of Gothenburg (SE)
- Corresponding author
- Cederlöf, Martin
- ORCID
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2014-09-12
- Volume
- 17
- Issue
- 3
- Pages
- 340-344
- ISSN
- 1398-5647 (ISSN-L)
- OpenAlex
- W2056727697
- Cited by
- 52
- References
- 27
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 11 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 6 · 2015: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Swedish Research Council Formas (2011-2492)
- SIMSAM (340-2013-5867)
- Swedish Research Council for Health, Working Life and Welfare.
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- Darier disease, bipolar disorder, schizophrenia, ATP2A2 gene, genetic susceptibility, familial aggregation, first-degree relatives, genetic association, skin diseases
- MeSH terms
- Bipolar Disorder, Humans, Darier Disease, Pedigree, Registries, Risk, Schizophrenia, Sweden, Cohort Studies, Odds Ratio, Genetic Predisposition to Disease, Sarcoplasmic Reticulum Calcium-Transporting ATPases
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