Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4
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We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
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Large-scale meta-analysis of GWAS has obtained statistically convincing evidence for common variants in schizophrenia and bipolar disorder.
“Large Scale meta-analysis of GWAS has obtained statistically convincing evidence for common variants in schizophrenia (Ripke et al., 2011) and bipolar disorder (Sklar et al., 2011).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Sklar et al., 2011
Activity of voltage-gated calcium ions was implicated in a pathway analysis of a bipolar disorder GWAS data set.
“Activity of voltage-gated calcium ions was also implicated in a pathway analysis of a bipolar disorder GWAS data set11”
From Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways (2015) · cites this paper as [11]
Results from SGENE+ implicate NRGN (neurogranin) which may act as a calcium sensor.
“Further, results from SGENE+ 60 implicate NRGN (neurogranin) which may act as a calcium sensor. 61”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [60]
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- Authors
- Psychiatric GWAS Consortium Bipolar Disorder Working Group, Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., Edenberg, H. J., Nurnberger, J. I., Rietschel, M., Blackwood, D., Corvin, A., Flickinger, M., Guan, W., Mattingsdal, M., McQuillin, A., Kwan, P., Wienker, T. F., Daly, M., Dudbridge, F., Holmans, P. A., Lin, D., Burmeister, M., Greenwood, T. A., Hamshere, M. L., Muglia, P., Smith, E. N., Zandi, P. P., Nievergelt, C. M., McKinney, R., Shilling, P. D., Schork, N. J., Bloss, C. S., Foroud, T., Koller, D. L., Gershon, E. S., Liu, C., Badner, J. A., Scheftner, W. A., Lawson, W. B., Nwulia, E. A., Hipolito, M., Coryell, W., Rice, J., Byerley, W., McMahon, F. J., Schulze, T. G., Berrettini, W., Lohoff, F. W., Potash, J. B., Mahon, P. B., McInnis, M. G., Zöllner, S., Zhang, P., Craig, D. W., Szelinger, S., Barrett, T. B., Breuer, R., Meier, S., Strohmaier, J., Witt, S. H., Tozzi, F., Farmer, A., McGuffin, P., Strauss, J., Xu, W., Kennedy, J. L., Vincent, J. B., Matthews, K., Day, R., Ferreira, M. A., O'Dushlaine, C., Perlis, R., Raychaudhuri, S., Ruderfer, D., Lee, P. H., Smoller, J. W., Li, J., Absher, D., Bunney, W. E., Barchas, J. D., Schatzberg, A. F., Jones, E. G., Meng, F., Thompson, R. C., Watson, S. J., Myers, R. M., Akil, H., Boehnke, M., Chambert, K., Moran, J., Scolnick, E., Djurovic, S., Melle, I., Morken, G., Gill, M., Morris, D., Quinn, E., Mühleisen, T. W., Degenhardt, F. A., Mattheisen, M., Schumacher, J., Maier, W., Steffens, M., Propping, P., Nöthen, M. M., Anjorin, A., Bass, N., Gurling, H., Kandaswamy, R., Lawrence, J., McGhee, K., McIntosh, A., McLean, A. W., Muir, W. J., Pickard, B. S., Breen, G., St. Clair, D., Caesar, S., Gordon-Smith, K., Jones, L., Fraser, C., Green, E. K., Grozeva, D., Jones, I. R., Kirov, G., Moskvina, V., Nikolov, I., O'Donovan, M. C., Owen, M. J., Collier, D. A., Elkin, A., Williamson, R., Young, A. H., Ferrier, I. N., Stefansson, K., Stefansson, H., Þorgeirsson, Þ., Steinberg, S., Gustafsson, Ó., Bergen, S. E., Nimgaonkar, V., Hultman, C., Landén, M., Lichtenstein, P., Sullivan, P., Schalling, M., Osby, U., Backlund, L., Frisén, L., Langstrom, N., Jamain, S., Leboyer, M., Etain, B., Bellivier, F., Petursson, H., Sigur∂sson, E., Müller-Mysok, B., Lucae, S., Schwarz, M., Fullerton, J. M., Schofield, P. R., Martin, N., Montgomery, G. W., Lathrop, M., Óskarsson, H., Bauer, M., Wright, A., Mitchell, P. B., Hautzinger, M., Reif, A., Kelsoe, J. R., & Purcell, S. M.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- University of Michigan (US)
- Oslo University Hospital (NO)
- University of Bonn (DE)
- Cardiff University (GB)
- Indiana University Indianapolis (US)
- Heidelberg University (DE)
- Western General Hospital (GB)
- Trinity College Dublin (IE)
- University of Oslo (NO)
- University College London (GB)
- University of London (GB)
- University of North Carolina at Chapel Hill (US)
- University of California San Diego (US)
- GlaxoSmithKline (Italy) (IT)
- Scripps Health (US)
- Johns Hopkins University (US)
- Scripps Research Institute (US)
- Indiana University School of Medicine (US)
- University of Chicago (US)
- Rush University Medical Center (US)
- Howard University (US)
- University of Iowa (US)
- Washington University in St. Louis (US)
- University of California, San Francisco (US)
- National Institutes of Health (US)
- University of Pennsylvania (US)
- Translational Genomics Research Institute (US)
- Portland VA Medical Center (US)
- King's College London (GB)
- Centre for Addiction and Mental Health (CA)
- Princess Margaret Cancer Centre (CA)
- University of Dundee (GB)
- HudsonAlpha Institute for Biotechnology (US)
- University of California, Irvine (US)
- Cornell University (US)
- Stanford Medicine (US)
- University of California, Davis (US)
- Norwegian University of Science and Technology (NO)
- University of Birmingham (GB)
- University of British Columbia (CA)
- deCODE Genetics (Iceland) (IS)
- University of Pittsburgh (US)
- Karolinska Institutet (SE)
- Inserm (FR)
- University of Iceland (IS)
- Max Planck Institute of Psychiatry (DE)
- UNSW Sydney (AU)
- QIMR Berghofer Medical Research Institute (AU)
- University Hospital Carl Gustav Carus (DE)
- Black Dog Institute (AU)
- University of Tübingen (DE)
- University of Würzburg (DE)
- Corresponding author
- Sklar, Pamela
- ORCID
- Sklar, Pamela
- Ripke, Stephan
- Scott, Laura J
- Andreassen, Ole A
- Cichon, Sven
- Craddock, Nick
- Edenberg, Howard J
- Rietschel, Marcella
- Blackwood, Douglas
- Corvin, Aiden
- Flickinger, Matthew
- Guan, Weihua
- Mattingsdal, Morten
- McQuillin, Andrew
- Daly, Mark
- Dudbridge, Frank
- Holmans, Peter A
- Burmeister, Margit
- Greenwood, Tiffany A
- Hamshere, Marian L
- Muglia, Pierandrea
- Smith, Erin N
- Zandi, Peter P
- Nievergelt, Caroline M
- Shilling, Paul D
- Schork, Nicholas J
- Bloss, Cinnamon S
- Foroud, Tatiana
- Gershon, Elliot S
- Liu, Chunyu
- Lawson, William B
- Nwulia, Evaristus A
- Coryell, William
- Rice, John
- McMahon, Francis J
- Schulze, Thomas G
- Berrettini, Wade
- Lohoff, Falk W
- Potash, James B
- Mahon, Pamela B
- McInnis, Melvin G
- Zöllner, Sebastian
- Craig, David W
- Barrett, Thomas B
- Meier, Sandra
- Witt, Stephanie H
- Tozzi, Federica
- McGuffin, Peter
- Xu, Wei
- Kennedy, James L
- Vincent, John B
- Matthews, Keith
- Ferreira, Manuel A
- Perlis, Roy
- Raychaudhuri, Soumya
- Ruderfer, Douglas
- Smoller, Jordan W
- Li, Jun
- Bunney, William E
- Barchas, Jack D
- Schatzberg, Alan F
- Jones, Edward G
- Meng, Fan
- Thompson, Robert C
- Watson, Stanley J
- Myers, Richard M
- Akil, Huda
- Boehnke, Michael
- Moran, Jennifer
- Djurovic, Srdjan
- Melle, Ingrid
- Morken, Gunnar
- Gill, Michael
- Morris, Derek
- Mühleisen, Thomas W
- Degenhardt, Franziska A
- Mattheisen, Manuel
- Schumacher, Johannes
- Steffens, Michael
- Nöthen, Markus M
- Kandaswamy, Radhika
- Lawrence, Jacob
- McIntosh, Andrew
- Breen, Gerome
- Jones, Lisa
- Fraser, Christine
- Green, Elaine K
- Grozeva, Detelina
- Jones, Ian R
- Kirov, George
- Owen, Michael J
- Collier, David A
- Young, Allan H
- Ferrier, I Nicol
- Steinberg, Stacy
- Bergen, Sarah E
- Nimgaonkar, Vishwajit
- Landén, Mikael
- Lichtenstein, Paul
- Sullivan, Patrick
- Schalling, Martin
- Backlund, Lena
- Frisén, Louise
- Jamain, Stéphane
- Leboyer, Marion
- Bellivier, Frank
- Lucae, Susanne
- Schwarz, Markus
- Fullerton, Janice M
- Schofield, Peter R
- Montgomery, Grant W
- Lathrop, Mark
- Bauer, Michael
- Mitchell, Philip B
- Hautzinger, Martin
- Reif, Andreas
- Kelsoe, John R
- Purcell, Shaun M
- Venue
- Nature Genetics
- Published
- 2011-09-18
- Volume
- 43
- Issue
- 10
- Pages
- 977-983
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3637176
- OpenAlex
- W1993588417
- Cited by
- 1,344
- References
- 30
- Citations by year
- 2026: 24 · 2025: 23 · 2024: 28 · 2023: 42 · 2022: 63 · 2021: 56 · 2020: 67 · 2019: 111 · 2018: 138 · 2017: 141 · 2016: 131 · 2015: 126 · 2014: 140 · 2013: 141 · 2012: 105
- FWCI
- 86.00
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-08-29)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- HAL (submittedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- UNC Libraries
- Funders
- Wellcome Trust
- Fondation pour la Recherche Médicale
- Norges Forskningsråd
- National Institutes of Health (5r01mh083738-03)
- National Institute of Mental Health (R01MH077139, R01MH059553, P50MH066392, MH081804, R01MH078151, R01-MH083738, MH 59553, U01MH094421, R01MH059567, R01MH071681, MH078151, R01MH081804, MH080372, R01MH074027, R01MH093500, K08MH080372, MH059567, R01MH080403)
- National Human Genome Research Institute (R01HG005827, T32HG000040)
- National Center for Research Resources (1U54RR025204)
- 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, genetic susceptibility, CACNA1C, calcium channels, intronic variants, schizophrenia, replication
- MeSH terms
- Alleles, Bipolar Disorder, Humans, Nuclear Proteins, Schizophrenia, Linkage Disequilibrium, Genome, Human, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Calcium Channels, L-Type, Databases, Genetic, Genome-Wide Association Study, Genetic Loci
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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