Schizophrenia as a Complex Trait: Evidence From a Meta-analysis of Twin Studies
Abstract
CONTEXT: There are many published twin studies of schizophrenia. Although these studies have been reviewed previously, to our knowledge, no review has provided quantitative summary estimates of the impact of genes and environment on liability to schizophrenia that also accounted for the different ascertainment strategies used. OBJECTIVE: To calculate meta-analytic estimates of heritability in liability and shared and individual-specific environmental effects from the pooled twin data. DATA SOURCES: We used a structured literature search to identify all published twin studies of schizophrenia, including MEDLINE, dissertation, and books-in-print searches. STUDY SELECTION: Of the 14 identified studies, 12 met the minimal inclusion criteria of systematic ascertainment. DATA SYNTHESIS: By using a multigroup twin model, we found evidence for substantial additive genetic effects-the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia-joint estimate, 11% (95% confidence interval, 3%-19%). CONCLUSIONS: Despite evidence of heterogeneity across studies, these meta-analytic results from 12 published twin studies of schizophrenia are consistent with a view of schizophrenia as a complex trait that results from genetic and environmental etiological influences. These results are broadly informative in that they provide no information about the specific identity of these etiological influences, but they do provide a component of a unifying empirical basis supporting the rationality of searches for underlying genetic and common environmental etiological factors.
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Schizophrenia is highly heritable.
“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 Sullivan et al., 2003
Heritability estimates for MDD (~40%) are lower than those for schizophrenia, bipolar disorder, and ADHD (all between 75% and 80%).
“the heritability estimates (~40%) are less than those for other neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder (all between 75% and 80%)”
From Epigenetics and depression (2019) · cites this paper as [6]
Schizophrenia has a lifetime risk of about 0.7% and heritability of 60-80% despite reduced reproductive fecundity.
“Schizophrenia is a psychiatric disorder with a lifetime risk of about 0.7%1 and a heritability of 60–80%2,3 despite greatly reduced reproductive fecundity4,5.”
From Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia (2016) · cites this paper as [2]
Estimates from two different methods indicated that the risk profile component for SCZ contributes between a quarter and a third of the overall variance in liability to SCZ, a substantial fraction of the 65-81% heritability of SCZ.
“Finally, estimates from two different methods indicated that the risk profile component for SCZ contributes between a quarter and a third of the overall variance in liability to SCZ, 69,130 a substantial fraction of the 65–81% heritability of SCZ. 179,180”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [179]
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- Authors
- Sullivan, P. F., Kendler, K. S., & Neale, M. C.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Sullivan, Patrick F.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2003-12-01
- Volume
- 60
- Issue
- 12
- Pages
- 1187
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W1963673462
- Cited by
- 2,356
- References
- 46
- Citations by year
- 2026: 69 · 2025: 81 · 2024: 94 · 2023: 129 · 2022: 110 · 2021: 116 · 2020: 163 · 2019: 111 · 2018: 131 · 2017: 175 · 2016: 148 · 2015: 147 · 2014: 149 · 2013: 126 · 2012: 122
- FWCI
- 17.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (K02MH001458, MH-01458)
- 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, heritability, twin studies, shared environment, additive genetic effects, complex traits, genetic etiology, environmental etiology
- MeSH terms
- Diseases in Twins, Humans, Risk Factors, Schizophrenia, Social Environment, Statistics as Topic, Twin Studies as Topic, Genetic Predisposition to Disease
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