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

Ösby, Urban; Sklar, Pamela; Ripke, Stephan; Scott, Laura J.; Andreassen, Ole A.; Cichon, Sven; Craddock, Nick; Thornorgeirsson, Thornorgeir; Edenberg, Howard J.; Nurnberger, John I.; Rietschel, Marcella; Blackwood, Douglas; Corvin, Aiden; Flickinger, Matthew; Wienker, Thomas F.; Guan, Weihua; Mattingsdal, Morten; McQuillin, Andrew; Kwan, Phoenix; Daly, Mark; Dudbridge, Frank; Holmans, Peter A.; Lin, Danyu; Burmeister, Margit; Zandi, Peter Pp; Zoellner, Sebastian; Greenwood, Tiffany A.; Hamshere, Marian L.; Muglia, Pierandrea; Smith, Erin N.; 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.; Zöllner, Sebastian; Lawson, William B.; Nwulia, Evaristus A.; Hipolito, Maria; Coryell, William; Rice, John P.; Zhang, Peng; Byerley, William; McMahon, Francis J.; Schulze, Thomas G.; Szelinger, Szabocls; Berrettini, Wade; Lohoff, Falk W.; Potash, James B.; Mcinnis, Melvin G.; Witt, Stephanie H.; Mahon, Pamela B.; Tozzi, Federica; Craig, David W.; McInnis, Mg G.; Barrett, Thomas B.; Xu, Wei; Breuer, René; Meier, Sandra; Strohmaier, Jana; Vincent, John B.; Ferreira, Manuel D. C.; Farmer, Anne; McGuffin, Peter; Strauss, John; Kennedy, James L.; Matthews, Keith; Day, Richard; Ferreira, Manuel A.; O'Dushlaine, Colm; Perlis, Roy; Lee, Phil H.; Raychaudhuri, Soumya; Thompson, Robert C.; Ruderfer, Douglas; Smoller, Jordan W.; Watson, Stanley J.; Hyoun, Phil L.; Li, Jun; Absher, Devin; Bunney, William E.; Schatzberg, Alan F.; Barchas, Jack D.; Muhleisen, Tw W.; Meng, Fan Guo; Jones, Edward G.; Myers, Richard M.; Nöthen, Markus M.; Akil, Huda; Boehnke, Michael; Chambert, Kim; Moran, Jennifer; Scolnick, Ed; Djurovic, Srdjan; Melle, Ingrid; Morken, Gunnar; Gill, Michael; Morris, Derek; Quinn, Emma; Muehleisen, Thomas W.; Mühleisen, Thomas W.; Degenhardt, Franziska A.; Noethen, Markus M.; Mattheisen, Manuel; Schumacher, Johannes; Þorgeirsson, Þorgeir; Mclean, Alan W.; Maier, Wolfgang; Steffens, Michael; Propping, Peter; Nöthen, Markus M.; Anjorin, Adebayo; Bass, Nick; McLean, Aw W.; Gurling, Hugh; Kandaswamy, Radhika; Lawrence, Jacob; McGhee, Kevin; McIntosh, Andrew; Muir, Walter J.; St Clair, David; Pickard, Benjamin S.; Williamson, Richard; Breen, Gerome; Young, Allan H.; O’Donovan, Michael; Caesar, Sian; Gordon-Smith, Katherine; Jones, Lisa; Fraser, Christine; Green, Elaine K.; Nicol Ferrier, I.; Grozeva, Detelina; Óskarsson, Högni; Jones, Ian R.; Kirov, George; Moskvina, Valentina; Nikolov, Ivan; O'Donovan, Michael C.; Owen, Michael J.; Collier, David A.; Elkin, Amanda; Porgeirsson, Porgeir; Ferrier, In Nicol; Stefansson, Kari; Stefansson, Hreinn; Steinberg, Stacy; Gustafsson, Omar; Bergen, Sarah E.; Nimgaonkar, Vishwajit; Hultman, Christina; Landén, Mikael; Sigur Sson, Engilbert; Lichtenstein, Paul; Sullivan, Patrick; Schalling, Martin; Osby, Urban; Backlund, Lena; Frisén, Louise; Wright, Adam; Langstrom, Niklas; Sigurosson, Engilbert; Jamain, Stéphane; Leboyer, Marion; Etain, Bruno; Muller-Mysok, B.; Bellivier, Frank; Petursson, Hannes; Sigur∂sson, Engilbert; Mueller-Mysok, Bertram; Müller-Mysok, Bertram; Lucae, Susanne; Schwarz, Markus; Fullerton, Janice M.; Schofield, Peter R.; Martin, Nick; Montgomery, Grant W.; Lathrop, Mark; Oskarsson, Högni; Bauer, Michael; Mitchell, Philip B.; Hautzinger, Martin; Reif, Andreas; Kelsoe, John R.; Psychiat Gwas Consortium Bipolar, D.; Purcell, Shaun M.; Swami, Meera

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Ole A. Andreassen
Ösby et al., 2011

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Nature Research, Nature Medicine, 10(17), p. 1199-1199, 2011

DOI: 10.1038/nm.2524

Nature Research, Nature Genetics, 10(43), p. 977-983

DOI: 10.1038/ng.943

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@article{Ösby2011,
  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 &lt; 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 x 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.},
  author = {Ösby, Urban and Sklar, Pamela and Ripke, Stephan and Scott, Laura J. and Andreassen, Ole A. and Cichon, Sven and Craddock, Nick and Thornorgeirsson, Thornorgeir and Edenberg, Howard J. and Nurnberger, John I. and Rietschel, Marcella and Blackwood, Douglas and Corvin, Aiden and Flickinger, Matthew and Wienker, Thomas F. and Guan, Weihua and Mattingsdal, Morten and McQuillin, Andrew and Kwan, Phoenix and Daly, Mark and Dudbridge, Frank and Holmans, Peter A. and Lin, Danyu and Burmeister, Margit and Zandi, Peter Pp and Zoellner, Sebastian and Greenwood, Tiffany A. and Hamshere, Marian L. and Muglia, Pierandrea and Smith, Erin N. and Nievergelt, Caroline M. and McKinney, Rebecca and Shilling, Paul D. and Schork, Nicholas J. and Bloss, Cinnamon S. and Foroud, Tatiana and Koller, Daniel L. and Gershon, Elliot S. and Liu, Chunyu and Badner, Judith A. and Scheftner, William A. and Zöllner, Sebastian and Lawson, William B. and Nwulia, Evaristus A. and Hipolito, Maria and Coryell, William and Rice, John P. and Zhang, Peng and Byerley, William and McMahon, Francis J. and Schulze, Thomas G. and Szelinger, Szabocls and Berrettini, Wade and Lohoff, Falk W. and Potash, James B. and Mcinnis, Melvin G. and Witt, Stephanie H. and Mahon, Pamela B. and Tozzi, Federica and Craig, David W. and McInnis, Mg G. and Barrett, Thomas B. and Xu, Wei and Breuer, René and Meier, Sandra and Strohmaier, Jana and Vincent, John B. and Ferreira, Manuel D. C. and Farmer, Anne and McGuffin, Peter and Strauss, John and Kennedy, James L. and Matthews, Keith and Day, Richard and Ferreira, Manuel A. and O'Dushlaine, Colm and Perlis, Roy and Lee, Phil H. and Raychaudhuri, Soumya and Thompson, Robert C. and Ruderfer, Douglas and Smoller, Jordan W. and Watson, Stanley J. and Hyoun, Phil L. and Li, Jun and Absher, Devin and Bunney, William E. and Schatzberg, Alan F. and Barchas, Jack D. and Muhleisen, Tw W. and Meng, Fan Guo and Jones, Edward G. and Myers, Richard M. and Nöthen, Markus M. and Akil, Huda and Boehnke, Michael and Chambert, Kim and Moran, Jennifer and Scolnick, Ed and Djurovic, Srdjan and Melle, Ingrid and Morken, Gunnar and Gill, Michael and Morris, Derek and Quinn, Emma and Muehleisen, Thomas W. and Mühleisen, Thomas W. and Degenhardt, Franziska A. and Noethen, Markus M. and Mattheisen, Manuel and Schumacher, Johannes and Þorgeirsson, Þorgeir and Mclean, Alan W. and Maier, Wolfgang and Steffens, Michael and Propping, Peter and Nöthen, Markus M. and Anjorin, Adebayo and Bass, Nick and McLean, Aw W. and Gurling, Hugh and Kandaswamy, Radhika and Lawrence, Jacob and McGhee, Kevin and McIntosh, Andrew and Muir, Walter J. and St Clair, David and Pickard, Benjamin S. and Williamson, Richard and Breen, Gerome and Young, Allan H. and O’Donovan, Michael and Caesar, Sian and Gordon-Smith, Katherine and Jones, Lisa and Fraser, Christine and Green, Elaine K. and Nicol Ferrier, I. and Grozeva, Detelina and Óskarsson, Högni and Jones, Ian R. and Kirov, George and Moskvina, Valentina and Nikolov, Ivan and O'Donovan, Michael C. and Owen, Michael J. and Collier, David A. and Elkin, Amanda and Porgeirsson, Porgeir and Ferrier, In Nicol and Stefansson, Kari and Stefansson, Hreinn and Steinberg, Stacy and Gustafsson, Omar and Bergen, Sarah E. and Nimgaonkar, Vishwajit and Hultman, Christina and Landén, Mikael and Sigur Sson, Engilbert and Lichtenstein, Paul and Sullivan, Patrick and Schalling, Martin and Osby, Urban and Backlund, Lena and Frisén, Louise and Wright, Adam and Langstrom, Niklas and Sigurosson, Engilbert and Jamain, Stéphane and Leboyer, Marion and Etain, Bruno and Muller-Mysok, B. and Bellivier, Frank and Petursson, Hannes and Sigur∂sson, Engilbert and Mueller-Mysok, Bertram and Müller-Mysok, Bertram and Lucae, Susanne and Schwarz, Markus and Fullerton, Janice M. and Schofield, Peter R. and Martin, Nick and Montgomery, Grant W. and Lathrop, Mark and Oskarsson, Högni and Bauer, Michael and Mitchell, Philip B. and Hautzinger, Martin and Reif, Andreas and Kelsoe, John R. and Psychiat Gwas Consortium Bipolar, D. and Purcell, Shaun M. and Swami, Meera},
  doi = {10.1038/nm.2524},
  journal = {Nature Genetics},
  month = {sep},
  pages = {977-983},
  title = {Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.},
  url = {https://www.nature.com/articles/ng.943.pdf},
  volume = {43},
  year = {2011}
}

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

Journal article published in 2011 by Urban Ösby, Pamela Sklar, Stephan Ripke, Laura J. Scott, Ole A. Andreassen

, Sven Cichon, Nick Craddock, Thornorgeir Thornorgeirsson, Howard J. Edenberg

, John I. Nurnberger, Marcella Rietschel, Douglas Blackwood, Aiden Corvin, Matthew Flickinger, Thomas F. Wienker and other authors. Urban Ösby, Pamela Sklar, Stephan Ripke, Laura J. Scott, Ole A. Andreassen

, Sven Cichon, Nick Craddock, Thornorgeir Thornorgeirsson, Howard J. Edenberg

, John I. Nurnberger, Marcella Rietschel, Douglas Blackwood, Aiden Corvin, Matthew Flickinger, Thomas F. Wienker, Weihua Guan, Morten Mattingsdal, Andrew McQuillin, Phoenix Kwan, Mark Daly, Frank Dudbridge, Peter A. Holmans, Danyu Lin, Margit Burmeister, Peter Pp Zandi, Sebastian Zoellner, Tiffany A. Greenwood, Marian L. Hamshere, Pierandrea Muglia, Erin N. Smith, Caroline M. Nievergelt

, Rebecca McKinney, Paul D. Shilling, Nicholas J. Schork, Cinnamon S. Bloss, Tatiana Foroud, Daniel L. Koller, Elliot S. Gershon, Chunyu Liu, Judith A. Badner, William A. Scheftner, Sebastian Zöllner, William B. Lawson, Evaristus A. Nwulia, Maria Hipolito, William Coryell, John P. Rice, Peng Zhang, William Byerley, Francis J. McMahon

, Thomas G. Schulze, Szabocls Szelinger, Wade Berrettini, Falk W. Lohoff, James B. Potash, Melvin G. Mcinnis, Stephanie H. Witt, Pamela B. Mahon, Federica Tozzi, David W. Craig, Mg G. McInnis, Thomas B. Barrett, Wei Xu, René Breuer, Sandra Meier, Jana Strohmaier, John B. Vincent, Manuel D. C. Ferreira, Anne Farmer, Peter McGuffin, John Strauss, James L. Kennedy, Keith Matthews, Richard Day, Manuel A. Ferreira, Colm O'Dushlaine, Roy Perlis, Phil H. Lee, Soumya Raychaudhuri, Robert C. Thompson, Douglas Ruderfer

, Jordan W. Smoller, Stanley J. Watson, Phil L. Hyoun, Jun Li, Devin Absher, William E. Bunney, Alan F. Schatzberg, Jack D. Barchas, Tw W. Muhleisen, Fan Guo Meng, Edward G. Jones, Richard M. Myers, Markus M. Nöthen, Huda Akil, Michael Boehnke, Kim Chambert, Jennifer Moran, Ed Scolnick, Srdjan Djurovic, Ingrid Melle, Gunnar Morken, Michael Gill, Derek Morris

, Emma Quinn, Thomas W. Muehleisen, Thomas W. Mühleisen, Franziska A. Degenhardt, Markus M. Noethen, Manuel Mattheisen

, Johannes Schumacher, Þorgeir Þorgeirsson, Alan W. Mclean, Wolfgang Maier, Michael Steffens, Peter Propping, Markus M. Nöthen, Adebayo Anjorin, Nick Bass, Aw W. McLean, Hugh Gurling, Radhika Kandaswamy, Jacob Lawrence, Kevin McGhee, Andrew McIntosh

, Walter J. Muir, David St Clair, Benjamin S. Pickard, Richard Williamson, Gerome Breen

, Allan H. Young, Michael O’Donovan, Sian Caesar, Katherine Gordon-Smith, Lisa Jones, Christine Fraser, Elaine K. Green, I. Nicol Ferrier, Detelina Grozeva, Högni Óskarsson, Ian R. Jones, George Kirov, Valentina Moskvina, Ivan Nikolov, Michael C. O'Donovan

, Michael J. Owen, David A. Collier, Amanda Elkin, Porgeir Porgeirsson, In Nicol Ferrier, Kari Stefansson, Hreinn Stefansson, Stacy Steinberg, Omar Gustafsson, Sarah E. Bergen, Vishwajit Nimgaonkar, Christina Hultman, Mikael Landén, Engilbert Sigur Sson, Paul Lichtenstein, Patrick Sullivan, Martin Schalling, Urban Osby, Lena Backlund, Louise Frisén, Adam Wright, Niklas Langstrom, Engilbert Sigurosson, Stéphane Jamain, Marion Leboyer, Bruno Etain, B. Muller-Mysok, Frank Bellivier, Hannes Petursson, Engilbert Sigur∂sson, Bertram Mueller-Mysok, Bertram Müller-Mysok, Susanne Lucae, Markus Schwarz, Janice M. Fullerton, Peter R. Schofield

, Nick Martin, Grant W. Montgomery, Mark Lathrop, Högni Oskarsson, Michael Bauer, Philip B. Mitchell, Martin Hautzinger, Andreas Reif, John R. Kelsoe, D. Psychiat Gwas Consortium Bipolar, Shaun M. Purcell, Meera Swami

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

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