The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia
Open accessAbstract
Molecular genetic analysis offers opportunities to advance our understanding of the nosological relationship between psychiatric diagnostic categories in general, and the mood and psychotic disorders in particular. Strong evidence (P=7.0 × 10(-7)) of association at the polymorphism rs1006737 (within CACNA1C, the gene encoding the α-1C subunit of the L-type voltage-gated calcium channel) with the risk of bipolar disorder (BD) has recently been reported in a meta-analysis of three genome-wide association studies of BD, including our BD sample (N=1868) studied within the Wellcome Trust Case Control Consortium. Here, we have used our UK case samples of recurrent major depression (N=1196) and schizophrenia (N=479) and UK non-psychiatric comparison groups (N=15316) to examine the spectrum of phenotypic effect of the bipolar risk allele at rs1006737. We found that the risk allele conferred increased risk for schizophrenia (P=0.034) and recurrent major depression (P=0.013) with similar effect sizes to those previously observed in BD (allelic odds ratio ∼1.15). Our findings are evidence of some degree of overlap in the biological underpinnings of susceptibility to mental illness across the clinical spectrum of mood and psychotic disorders, and show that at least some loci can have a relatively general effect on susceptibility to diagnostic categories, as currently defined. Our findings will contribute to a better understanding of the pathogenesis of major psychiatric illness, and such knowledge should be useful in providing an etiological rationale for shaping psychiatric nosology, which is currently reliant entirely on descriptive clinical data.
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An intronic SNP of CACNA1C (rs1006737) appears in multiple neuropsychiatric disorders, including ASD.
“This effort has begun for an intronic SNP of CACNA1C (rs1006737) that crops up in multiple neuropsychiatric disorders (Ferreira et al., 2008; Green et al., 2010; Moskvina et al., 2009; Nyegaard et al., 2010), including ASD (Li et al., 2015).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Green et al., 2010
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- Authors
- Wellcome Trust Case Control Consortium, Green, E. K., Grozeva, D., Jones, I., Jones, L., Kirov, G., Caesar, S., Gordon-Smith, K., Fraser, C., Forty, L., Russell, E., Hamshere, M. L., Moskvina, V, Nikolov, I., Farmer, A., McGuffin, P., Holmans, P. A., Owen, M. J., O'Donovan, M. C., & Craddock, N.
- Affiliations
- Cardiff University (GB)
- University of Birmingham (GB)
- King's College London (GB)
- Corresponding author
- Craddock, N
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2009-07-21
- Volume
- 15
- Issue
- 10
- Pages
- 1016-1022
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3011210
- OpenAlex
- W2098525901
- Cited by
- 526
- References
- 30
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 10 · 2023: 21 · 2022: 25 · 2021: 40 · 2020: 24 · 2019: 33 · 2018: 29 · 2017: 36 · 2016: 33 · 2015: 30 · 2014: 39 · 2013: 56 · 2012: 40
- FWCI
- 25.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- 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
- CACNA1C, rs1006737, bipolar disorder, recurrent major depressive disorder, schizophrenia, L-type calcium channels, genetic susceptibility, psychiatric classification, mood disorders, psychosis, shared genetic risk
- MeSH terms
- Adult, Alleles, Bipolar Disorder, Major Depressive Disorder, Female, Genotype, United Kingdom, Humans, Male, Middle Aged, Phenotype, Recurrence, Risk Factors, Schizophrenia, Calcium Channels, L-Type
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