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

Rikke Hilker, Dorte Helenius, Birgitte Fagerlund, Axel Skytthe, Kaare Christensen, Thomas M Werge, Merete Nordentoft, Birte Glenthøj

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalBiological Psychiatry
Volume83
Issue number6
Pages (from-to)492-498
ISSN0006-3223
DOIs
Publication statusPublished - 2018

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Monozygotic Twins
Dizygotic Twins
Twin Studies
Research

Keywords

  • Censoring
  • Concordance
  • Heritability
  • Register
  • Schizophrenia
  • Twin study

Cite this

Hilker, Rikke ; Helenius, Dorte ; Fagerlund, Birgitte ; Skytthe, Axel ; Christensen, Kaare ; Werge, Thomas M ; Nordentoft, Merete ; Glenthøj, Birte. / Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register. In: Biological Psychiatry. 2018 ; Vol. 83, No. 6. pp. 492-498.
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title = "Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register",
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.",
keywords = "Censoring, Concordance, Heritability, Register, Schizophrenia, Twin study, Censoring, Concordance, Heritability, Register, Schizophrenia, Twin study",
author = "Rikke Hilker and Dorte Helenius and Birgitte Fagerlund and Axel Skytthe and Kaare Christensen and Werge, {Thomas M} and Merete Nordentoft and Birte Glenth{\o}j",
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year = "2018",
doi = "10.1016/j.biopsych.2017.08.017",
language = "English",
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Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register. / Hilker, Rikke; Helenius, Dorte; Fagerlund, Birgitte; Skytthe, Axel; Christensen, Kaare; Werge, Thomas M; Nordentoft, Merete; Glenthøj, Birte.

In: Biological Psychiatry, Vol. 83, No. 6, 2018, p. 492-498.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register

AU - Hilker, Rikke

AU - Helenius, Dorte

AU - Fagerlund, Birgitte

AU - Skytthe, Axel

AU - Christensen, Kaare

AU - Werge, Thomas M

AU - Nordentoft, Merete

AU - Glenthøj, Birte

N1 - Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Censoring

KW - Concordance

KW - Heritability

KW - Register

KW - Schizophrenia

KW - Twin study

KW - Censoring

KW - Concordance

KW - Heritability

KW - Register

KW - Schizophrenia

KW - Twin study

U2 - 10.1016/j.biopsych.2017.08.017

DO - 10.1016/j.biopsych.2017.08.017

M3 - Journal article

VL - 83

SP - 492

EP - 498

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 6

ER -