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Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

Sklar, Pamela
; 
Ripke, Stephan
; 
Scott, Laura J
; 
Andreassen, Ole A
; 
Cichon, Sven
; 
Craddock, Nick
; 
Edenberg, Howard J
; 
Nurnberger, John I
; 
Rietschel, Marcella
; 
Blackwood, Douglas
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Author
Sklar, Pamela
 Ripke, Stephan
 Scott, Laura J
 Andreassen, Ole A
 Cichon, Sven
 Craddock, Nick
 Edenberg, Howard J
 Nurnberger, John I
 Rietschel, Marcella
 Blackwood, Douglas
 Corvin, Aiden
 Flickinger, Matthew
 Guan, Weihua
 Mattingsdal, Morten
 McQuillin, Andrew
 Kwan, Phoenix
 Wienker, Thomas F
 Daly, Mark
 Dudbridge, Frank
 Holmans, Peter A
 Lin, Danyu
 Burmeister, Margit
 Greenwood, Tiffany A
 Hamshere, Marian L
 Muglia, Pierandrea
 Smith, Erin N
 Zandi, Peter P
 Nievergelt, Caroline M
 McKinney, Rebecca
 Shilling, Paul D
 Schork, Nicholas J
 Bloss, Cinnamon S
 Foroud, Tatiana
 Koller, Daniel L
 Gershon, Elliot S
 Liu, Chunyu
 Badner, Judith A
 Scheftner, William A
 Lawson, William B
 Nwulia, Evaristus A
 Hipolito, Maria
 Coryell, William
 Rice, John
 Byerley, William
 McMahon, Francis J
 Schulze, Thomas G
 Berrettini, Wade
 Lohoff, Falk W
 Potash, James B
 Mahon, Pamela B
 McInnis, Melvin G
 Zöllner, Sebastian
 Zhang, Peng
 Craig, David W
 Szelinger, Szabocls
 Barrett, Thomas B
 Breuer, René
 Meier, Sandra
 Strohmaier, Jana
 Witt, Stephanie H
 Tozzi, Federica
 Farmer, Anne
 McGuffin, Peter
 Strauss, John
 Xu, Wei
 Kennedy, James L
 Vincent, John B
 Matthews, Keith
 Day, Richard
 Ferreira, Manuel A
 O'Dushlaine, Colm
 Perlis, Roy
 Raychaudhuri, Soumya
 Ruderfer, Douglas
 Hyoun, Phil L
 Smoller, Jordan W
 Li, Jun
 Absher, Devin
 Thompson, Robert C
 Meng, Fan Guo
 Schatzberg, Alan F
 Bunney, William E
 Barchas, Jack D
 Jones, Edward G
 Watson, Stanley J
 Myers, Richard M
 Akil, Huda
 Boehnke, Michael
 Chambert, Kim
 Moran, Jennifer
 Scolnick, Ed
 Djurovic, Srdjan
 Melle, Ingrid
 Morken, Gunnar
 Gill, Michael
 Morris, Derek
 Quinn, Emma
 Mühleisen, Thomas W
 Degenhardt, Franziska A
 Mattheisen, Manuel
 Schumacher, Johannes
 Maier, Wolfgang
 Steffens, Michael
 Propping, Peter
 Nöthen, Markus M
 Anjorin, Adebayo
 Bass, Nick
 Gurling, Hugh
 Kandaswamy, Radhika
 Lawrence, Jacob
 McGhee, Kevin
 McIntosh, Andrew
 McLean, Alan W
 Muir, Walter J
 Pickard, Benjamin S
 Breen, Gerome
 St Clair, David
 Caesar, Sian
 Gordon-Smith, Katherine
 Jones, Lisa
 Fraser, Christine
 Green, Elaine K
 Grozeva, Detelina
 Jones, Ian R
 Kirov, George
 Moskvina, Valentina
 Nikolov, Ivan
 O'Donovan, Michael C
 Owen, Michael J
 Collier, David A
 Elkin, Amanda
 Williamson, Richard
 Young, Allan H
 Ferrier, I Nicol
 Stefansson, Kari
 Stefansson, Hreinn
 Thornorgeirsson, Thornorgeir
 Steinberg, Stacy
 Gustafsson, Omar
 Bergen, Sarah E
 Nimgaonkar, Vishwajit
 Hultman, Christina
 Landén, Mikael
 Lichtenstein, Paul
 Sullivan, Patrick
 Schalling, Martin
 Osby, Urban
 Backlund, Lena
 Frisén, Louise
 Langstrom, Niklas
 Jamain, Stéphane
 Leboyer, Marion
 Etain, Bruno
 Bellivier, Frank
 Petursson, Hannes
 Sigur Sson, Engilbert
 Müller-Mysok, Bertram
 Lucae, Susanne
 Schwarz, Markus
 Schofield, Peter R
 Martin, Nick
 Montgomery, Grant W
 Lathrop, Mark
 Oskarsson, Högni
 Bauer, Michael
 Wright, Adam
 Mitchell, Philip B
 Hautzinger, Martin
 Reif, Andreas
 Kelsoe, John R
 Purcell, Shaun M
Advisors
Editors
Other Contributors
Departments
Division of Psychiatric Genomics, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. pamela.sklar@mssm.edu
Date
2011-10
Date Submitted
Keywords
Other Subjects
Subject Mesh
Alleles
Bipolar Disorder
Calcium Channels, L-Type
Case-Control Studies
Databases, Genetic
Genetic Loci
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Nuclear Proteins
Polymorphism, Single Nucleotide
Schizophrenia
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
URI
https://hdl.handle.net/10147/238795
Abstract
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.
Language
en
Citation
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. 2011, 43 (10):977-83 Nat. Genet.
ISSN
1546-1718
eISSN
ISBN
DOI
10.1038/ng.943
PMID
21926972
PMCID
Sponsorships
Funding Sources
Funding Amounts
Grant Identifiers
Methodology
Duration
Ethical Approval
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