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Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder
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To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.
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“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 Ferreira et al., 2008
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CACNA1C (rs1006737) is associated with schizophrenia
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Rare variants in neuronal excitability genes influence risk for bipolar disorder
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Brain Function in Carriers of a Genome-wide Supported Bipolar Disorder Variant
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Mitochondrial Oxidative Phosphorylation System (OXPHOS) Deficits in Schizophrenia
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Metadata
- Authors
- Wellcome Trust Case Control Consortium, Ferreira, M. A. R., O'Donovan, M. C., Meng, Y. A., Jones, I. R., Ruderfer, D. M., Jones, L., Fan, J., Kirov, G., Perlis, R. H., Green, E. K., Smoller, J. W., Grozeva, D., Stone, J., Nikolov, I., Chambert, K., Hamshere, M. L., Nimgaonkar, V. L., Moskvina, V., Thase, M. E., Caesar, S., Sachs, G. S., Franklin, J., Gordon-Smith, K., Ardlie, K. G., Gabriel, S. B., Fraser, C., Blumenstiel, B., Defelice, M., Breen, G., Gill, M., Morris, D. W., Elkin, A., Muir, W. J., McGhee, K. A., Williamson, R., MacIntyre, D. J., MacLean, A. W., St Clair, D., Robinson, M., Van Beck, M., Pereira, A. C. P., Kandaswamy, R., McQuillin, A., Collier, D. A., Bass, N. J., Young, A. H., Lawrence, J., Nicol Ferrier, I., Anjorin, A., Farmer, A., Curtis, D., Scolnick, E. M., McGuffin, P., Daly, M. J., Corvin, A. P., Holmans, P. A., Blackwood, D. H., Gurling, H. M., Owen, M. J., Purcell, S. M., Sklar, P., & Craddock, N.
- Affiliations
- Broad Institute (US)
- Cardiff University (GB)
- University of Birmingham (GB)
- University of Pittsburgh (US)
- University of Pittsburgh Medical Center (US)
- Harvard University (US)
- King's College London (GB)
- Trinity College Dublin (IE)
- Royal Edinburgh Hospital (GB)
- University College London (GB)
- University of British Columbia (CA)
- Corresponding author
- Sklar, Pamela
- Craddock, Nick
- ORCID
- Ferreira, Manuel A R
- Meng, Yan A
- Jones, Ian R
- Ruderfer, Douglas M
- Jones, Lisa
- Fan, Jinbo
- Kirov, George
- Perlis, Roy H
- Green, Elaine K
- Smoller, Jordan W
- Grozeva, Detelina
- Hamshere, Marian L
- Nimgaonkar, Vishwajit L
- Ardlie, Kristin G
- Gabriel, Stacey B
- Fraser, Christine
- Defelice, Matthew
- Breen, Gerome
- Gill, Michael
- Morris, Derek W
- MacIntyre, Donald J
- Pereira, Ana C P
- Kandaswamy, Radhika
- McQuillin, Andrew
- Collier, David A
- Bass, Nicholas J
- Young, Allan H
- Lawrence, Jacob
- Curtis, David
- Scolnick, Edward M
- McGuffin, Peter
- Daly, Mark J
- Corvin, Aiden P
- Holmans, Peter A
- Blackwood, Douglas H
- Owen, Michael J
- Purcell, Shaun M
- Sklar, Pamela
- Craddock, Nick
- Venue
- Nature Genetics
- Published
- 2008-08-17
- Volume
- 40
- Issue
- 9
- Pages
- 1056-1058
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2703780
- OpenAlex
- W2127442418
- Cited by
- 1,237
- References
- 15
- Citations by year
- 2026: 26 · 2025: 36 · 2024: 33 · 2023: 27 · 2022: 40 · 2021: 49 · 2020: 53 · 2019: 47 · 2018: 54 · 2017: 70 · 2016: 75 · 2015: 82 · 2014: 116 · 2013: 105 · 2012: 101
- FWCI
- 75.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Wellcome Trust (077011, 082371, 076113)
- Broad Institute
- Sylvan C. Herman Foundation
- Science Foundation Ireland
- National Institutes of Health (n01mh80001-12-0-0, 6u54rr020278-06)
- Medical Research Council (G0500791, G9623693N)
- National Institute of Mental Health (MH067288, N01-MH80001, MH063445, MH062137, R01MH067288, R01MH063445, R01MH063420, N01 MH080001, MH63420, R01MH062137)
- National Center for Research Resources (U54-RR020278)
- 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, ANK3, CACNA1C, ankyrin-G, L-type calcium channels, genetic susceptibility loci, channelopathies, rs1006737, disease risk variants
- MeSH terms
- Bipolar Disorder, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 15, Humans, Logistic Models, Ankyrins, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Calcium Channels, L-Type, Genome-Wide Association Study
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