Cited by 615Schizophrenia research and treatmentGenetic Associations and EpidemiologyBipolar Disorder and Treatment

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Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register

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Hilker, Rikke, Helenius, Dorte, Fagerlund, Birgitte, Skytthe, Axel, Christensen, Kaare, Werge, Thomas M., Nordentoft, Merete, Glenthøj, Birte·2018·Biological Psychiatry

DOI 10.1016/j.biopsych.2017.08.017

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Abstract

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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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: Helenius, Dorte
Fagerlund, Birgitte
Skytthe, Axel
Christensen, Kaare
Werge, Thomas M.
Nordentoft, Merete
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2018-03
Volume: 83
Issue: 6
Pages: 492-498
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2017.08.017
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: green
portal.findresearcher.sdu.dk
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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Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register

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