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Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register
Open accessAbstract
Background Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology.Methods Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs). Twins were followed until June 1, 2011. Liability threshold models adjusting for censoring with inverse probability weighting were used to estimate probandwise concordance rates and heritability of the diagnoses of SZ and SZ spectrum disorders.Results The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%).Conclusions The key strength of this study is the application of a novel statistical method accounting for censoring in the follow-up period to a nationwide twin sample. The estimated 79% heritability of SZ is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader phenotype of SZ spectrum disorders. The low concordance rate of 33% in monozygotic twins demonstrates that illness vulnerability is not solely indicated by genetic factors.
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“Schizophrenia is highly heritable (Hilker et al., 2018; Sullivan et al., 2003)”
From DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia (2021) · cites this paper as Hilker et al., 2018
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Metadata
- Authors
- Hilker, R., Helenius, D., Fagerlund, B., Skytthe, A., Christensen, K., Werge, T. M., Nordentoft, M., & Glenthøj, B.
- Affiliations
- University of Copenhagen (DK)
- Sankt Hans Hospital (DK)
- Mental Health Services (DK)
- University of Southern Denmark (DK)
- Corresponding author
- Hilker, Rikke
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 83
- Issue
- 6
- Pages
- 492-498
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2751739125
- Cited by
- 615
- References
- 41
- Citations by year
- 2026: 41 · 2025: 74 · 2024: 88 · 2023: 116 · 2022: 83 · 2021: 70 · 2020: 69 · 2019: 47 · 2018: 23
- FWCI
- 31.45
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc-nd)
- Funders
- Lundbeckfonden (R155-2013-16337, R155-2014-1724, R248‐2017‐2003)
- Region Hovedstaden
- Faculty of Health and Medical Sciences, University of Western Australia
- H. Lundbeck A/S
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- schizophrenia, schizophrenia spectrum disorders, heritability, twin concordance, monozygotic twins, dizygotic twins, liability threshold model, inverse probability weighting, censoring, genetic risk, environmental risk factors
- MeSH terms
- Adult, Denmark, Diseases in Twins, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Registries, Risk Factors, Schizophrenia, Twins, Dizygotic, Twins, Monozygotic, Genetic Predisposition to Disease, Young Adult, Gene-Environment Interaction
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