The Heritability of Bipolar Affective Disorder and the Genetic Relationship to Unipolar Depression
Abstract
BACKGROUND: Twin studies of bipolar affective disorder (BPD) have either been small or have not used explicit diagnostic criteria. There has been little use of genetic model fitting and no analyses to explore the etiological overlap with unipolar depression (UPD). METHODS: Sixty-seven twin pairs, 30 monozygotic and 37 dizygotic, in which the proband had BPD were ascertained, and lifetime diagnoses were made using DSM-IV criteria. Univariate models were applied to estimate the contribution of additive genetic and environmental effects. Bipolar data were then combined with those from 68 monozygotic and 109 dizygotic pairs in which the proband had UPD. Two models were explored: a classic 2-threshold approach, in which BPD and UPD occupy the same continuum of liability but differ in severity, and a correlated liability model of mania and depression. RESULTS: Heritability of BPD was estimated at 85% (95% confidence interval [CI], 0.73-0.93) using narrow concordance and 89% (95% CI, 0.61-1.0) using broad concordance, with no shared environmental effects detected. A 2-threshold model was an unsatisfactory fit. Fitting a correlated liability model revealed a genetic correlation of 0.65 (95% CI, 0.58-0.75) between mania and depression and a correlation of 0.59 (95% CI, 0.15-0.84) for nonfamilial environment. Approximately 71% of the genetic variance for mania was not shared with depression. CONCLUSIONS: As defined by the DSM-IV, BPD is highly heritable. There are substantial genetic and nonshared environmental correlations between mania and depression, but most of the genetic variance in liability to mania is specific to the manic syndrome.
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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 [7]
Bipolar disorder is a genetic disorder with 85-89% heritability.
“BD is a genetic disorder, with 85–89% heritability114, however, no causal “smoking gun” gene has yet been identified.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [114]
A strong inheritable genetic component might be involved in the pathogenesis of the affective disorders.
“In fact, it is now well accepted that a strong inheritable genetic component might be involved in the pathogenesis of the affective disorders [187].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [187]
A variety of genes have been shown to be involved in affective disorders development.
“In this way, a variety of genes have been shown to be involved in affective disorders development (reviewed by [187]).”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [187]
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- Authors
- McGuffin, P., Rijsdijk, F., Andrew, M., Sham, P., Katz, R., & Cardno, A.
- Affiliations
- King's College London (GB)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2003-05-01
- Volume
- 60
- Issue
- 5
- Pages
- 497
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2064554173
- Cited by
- 1,243
- References
- 21
- Citations by year
- 2026: 28 · 2025: 38 · 2024: 45 · 2023: 38 · 2022: 42 · 2021: 88 · 2020: 62 · 2019: 55 · 2018: 53 · 2017: 66 · 2016: 87 · 2015: 66 · 2014: 63 · 2013: 70 · 2012: 72
- FWCI
- 16.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- King's College London
- Menzies Centre for Australian Studies, King's College London, University of London
- National Institute of Mental Health (MH-44359, R01MH044359)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar disorder, major depressive disorder, heritability, twin concordance, genetic correlation, mania, depression, nonshared environment, genetic variance
- MeSH terms
- Bipolar Disorder, Depressive Disorder, Diseases in Twins, Family, Humans, London, Models, Genetic, Registries, Severity of Illness Index, Social Environment, Twins, Dizygotic, Twins, Monozygotic, Confidence Intervals, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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