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

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

doi:10.1038/ng.943

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

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

School of Medicine

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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 × 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.

Original language	English (US)
Pages (from-to)	977-985
Number of pages	9
Journal	Nature genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.943
State	Published - Oct 2011

ASJC Scopus subject areas

Genetics

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10.1038/ng.943

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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., ... Purcell, S. M. (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature genetics, 43(10), 977-985. https://doi.org/10.1038/ng.943

Sklar, P, Ripke, S, Scott, LJ, Andreassen, OA, Cichon, S, Craddock, N, Edenberg, HJ, Nurnberger, JI, Rietschel, M, Blackwood, D, Corvin, A, Flickinger, M, Guan, W, Mattingsdal, M, McQuillin, A, Kwan, P, Wienker, TF, Daly, M, Dudbridge, F, Holmans, PA, Lin, D, Burmeister, M, Greenwood, TA, Hamshere, ML, Muglia, P, Smith, EN, Zandi, PP, Nievergelt, CM, McKinney, R, Shilling, PD, Schork, NJ, Bloss, CS, Foroud, T, Koller, DL, Gershon, ES, Liu, C, Badner, JA, Scheftner, WA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Rice, J, Byerley, W, McMahon, FJ, Schulze, TG, Berrettini, W, Lohoff, FW, Potash, JB, Mahon, PB, McInnis, MG, Zöllner, S, Zhang, P, Craig, DW, Szelinger, S, Barrett, TB, Breuer, R, Meier, S, Strohmaier, J, Witt, SH, Tozzi, F, Farmer, A, McGuffin, P, Strauss, J, Xu, W, Kennedy, JL, Vincent, JB, Matthews, K, Day, R, Ferreira, MA, O'Dushlaine, C, Perlis, R, Raychaudhuri, S, Ruderfer, D, Lee, PH, Smoller, JW, Li, J, Absher, D, Bunney, WE, Barchas, JD, Schatzberg, AF, Jones, EG, Meng, F, Thompson, RC, Watson, SJ, Myers, RM, Akil, H, Boehnke, M, Chambert, K, Moran, J, Scolnick, E, Djurovic, S, Melle, I, Morken, G, Gill, M, Morris, D, Quinn, E, Mühleisen, TW, Degenhardt, FA, Mattheisen, M, Schumacher, J, Maier, W, Steffens, M, Propping, P, Nöthen, MM, Anjorin, A, Bass, N, Gurling, H, Kandaswamy, R, Lawrence, J, McGhee, K, McIntosh, A, McLean, AW, Muir, WJ, Pickard, BS, Breen, G, St. Clair, D, Caesar, S, Gordon-Smith, K, Jones, L, Fraser, C, Green, EK, Grozeva, D, Jones, IR, Kirov, G, Moskvina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Williamson, R, Young, AH, Nicol Ferrier, I, Stefansson, K, Stefansson, H, Porgeirsson, P, Steinberg, S, Gustafsson, Ó, Bergen, SE, 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, Sigurdsson, E, Müller-Mysok, B, Lucae, S, Schwarz, M, Fullerton, JM, Schofield, PR, Martin, N, Montgomery, GW, Lathrop, M, Óskarsson, H, Bauer, M, Wright, A, Mitchell, PB, Hautzinger, M, Reif, A, Kelsoe, JR & Purcell, SM 2011, 'Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4', Nature genetics, vol. 43, no. 10, pp. 977-985. https://doi.org/10.1038/ng.943

@article{1f3b4c6250ec4f2db9cf2dff2991b1ee,

title = "Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4",

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.",

author = "Pamela Sklar and Stephan Ripke and Scott, {Laura J.} and Andreassen, {Ole A.} and Sven Cichon and Nick Craddock and Edenberg, {Howard J.} and Nurnberger, {John I.} and Marcella Rietschel and Douglas Blackwood and Aiden Corvin and Matthew Flickinger and Weihua Guan and Morten Mattingsdal and Andrew McQuillin and Phoenix Kwan and Wienker, {Thomas F.} and Mark Daly and Frank Dudbridge and Holmans, {Peter A.} and Danyu Lin and Margit Burmeister and Greenwood, {Tiffany A.} and Hamshere, {Marian L.} and Pierandrea Muglia and Smith, {Erin N.} and Zandi, {Peter P.} and Nievergelt, {Caroline M.} and Rebecca McKinney and Shilling, {Paul D.} and Schork, {Nicholas J.} and Bloss, {Cinnamon S.} and Tatiana Foroud and Koller, {Daniel L.} and Gershon, {Elliot S.} and Chunyu Liu and Badner, {Judith A.} and Scheftner, {William A.} and Lawson, {William B.} and Nwulia, {Evaristus A.} and Maria Hipolito and William Coryell and John Rice and William Byerley and McMahon, {Francis J.} and Schulze, {Thomas G.} and Wade Berrettini and Lohoff, {Falk W.} and Potash, {James B.} and Mahon, {Pamela B.} and McInnis, {Melvin G.} and Sebastian Z{\"o}llner and Peng Zhang and Craig, {David W.} and Szabocls Szelinger and Barrett, {Thomas B.} and Ren{\'e} Breuer and Sandra Meier and Jana Strohmaier and Witt, {Stephanie H.} and Federica Tozzi and Anne Farmer and Peter McGuffin and John Strauss and Wei Xu and Kennedy, {James L.} and Vincent, {John B.} and Keith Matthews and Richard Day and Ferreira, {Manuel A.} and Colm O'Dushlaine and Roy Perlis and Soumya Raychaudhuri and Douglas Ruderfer and Lee, {Phil H.} and Smoller, {Jordan W.} and Jun Li and Devin Absher and Bunney, {William E.} and Barchas, {Jack D.} and Schatzberg, {Alan F.} and Jones, {Edward G.} and Fan Meng and Thompson, {Robert C.} and Watson, {Stanley J.} and Myers, {Richard M.} and Huda Akil and Michael Boehnke and Kim Chambert and Jennifer Moran and Ed Scolnick and Srdjan Djurovic and Ingrid Melle and Gunnar Morken and Michael Gill and Derek Morris and Emma Quinn and M{\"u}hleisen, {Thomas W.} and Degenhardt, {Franziska A.} and Manuel Mattheisen and Johannes Schumacher and Wolfgang Maier and Michael Steffens and Peter Propping and N{\"o}then, {Markus M.} and Adebayo Anjorin and Nick Bass and Hugh Gurling and Radhika Kandaswamy and Jacob Lawrence and Kevin McGhee and Andrew McIntosh and McLean, {Alan W.} and Muir, {Walter J.} and Pickard, {Benjamin S.} and Gerome Breen and {St. Clair}, David and Sian Caesar and Katherine Gordon-Smith and Lisa Jones and Christine Fraser and Green, {Elaine K.} and Detelina Grozeva and Jones, {Ian R.} and George Kirov and Valentina Moskvina and Ivan Nikolov and O'Donovan, {Michael C.} and Owen, {Michael J.} and Collier, {David A.} and Amanda Elkin and Richard Williamson and Young, {Allan H.} and {Nicol Ferrier}, I. and Kari Stefansson and Hreinn Stefansson and Porgeir Porgeirsson and Stacy Steinberg and {\'O}mar Gustafsson and Bergen, {Sarah E.} and Vishwajit Nimgaonkar and Christina Hultman and Mikael Land{\'e}n and Paul Lichtenstein and Patrick Sullivan and Martin Schalling and Urban Osby and Lena Backlund and Louise Fris{\'e}n and Niklas Langstrom and St{\'e}phane Jamain and Marion Leboyer and Bruno Etain and Frank Bellivier and Hannes Petursson and Engilbert Sigurdsson and Bertram M{\"u}ller-Mysok and Susanne Lucae and Markus Schwarz and Fullerton, {Janice M.} and Schofield, {Peter R.} and Nick Martin and Montgomery, {Grant W.} and Mark Lathrop and H{\"o}gni {\'O}skarsson and Michael Bauer and Adam Wright and Mitchell, {Philip B.} and Martin Hautzinger and Andreas Reif and Kelsoe, {John R.} and Purcell, {Shaun M.}",

year = "2011",

month = oct,

doi = "10.1038/ng.943",

language = "English (US)",

volume = "43",

pages = "977--985",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "10",

}

TY - JOUR

T1 - Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4

AU - Sklar, Pamela

AU - Ripke, Stephan

AU - Scott, Laura J.

AU - Andreassen, Ole A.

AU - Cichon, Sven

AU - Craddock, Nick

AU - Edenberg, Howard J.

AU - Nurnberger, John I.

AU - Rietschel, Marcella

AU - Blackwood, Douglas

AU - Corvin, Aiden

AU - Flickinger, Matthew

AU - Guan, Weihua

AU - Mattingsdal, Morten

AU - McQuillin, Andrew

AU - Kwan, Phoenix

AU - Wienker, Thomas F.

AU - Daly, Mark

AU - Dudbridge, Frank

AU - Holmans, Peter A.

AU - Lin, Danyu

AU - Burmeister, Margit

AU - Greenwood, Tiffany A.

AU - Hamshere, Marian L.

AU - Muglia, Pierandrea

AU - Smith, Erin N.

AU - Zandi, Peter P.

AU - Nievergelt, Caroline M.

AU - McKinney, Rebecca

AU - Shilling, Paul D.

AU - Schork, Nicholas J.

AU - Bloss, Cinnamon S.

AU - Foroud, Tatiana

AU - Koller, Daniel L.

AU - Gershon, Elliot S.

AU - Liu, Chunyu

AU - Badner, Judith A.

AU - Scheftner, William A.

AU - Lawson, William B.

AU - Nwulia, Evaristus A.

AU - Hipolito, Maria

AU - Coryell, William

AU - Rice, John

AU - Byerley, William

AU - McMahon, Francis J.

AU - Schulze, Thomas G.

AU - Berrettini, Wade

AU - Lohoff, Falk W.

AU - Potash, James B.

AU - Mahon, Pamela B.

AU - McInnis, Melvin G.

AU - Zöllner, Sebastian

AU - Zhang, Peng

AU - Craig, David W.

AU - Szelinger, Szabocls

AU - Barrett, Thomas B.

AU - Breuer, René

AU - Meier, Sandra

AU - Strohmaier, Jana

AU - Witt, Stephanie H.

AU - Tozzi, Federica

AU - Farmer, Anne

AU - McGuffin, Peter

AU - Strauss, John

AU - Xu, Wei

AU - Kennedy, James L.

AU - Vincent, John B.

AU - Matthews, Keith

AU - Day, Richard

AU - Ferreira, Manuel A.

AU - O'Dushlaine, Colm

AU - Perlis, Roy

AU - Raychaudhuri, Soumya

AU - Ruderfer, Douglas

AU - Lee, Phil H.

AU - Smoller, Jordan W.

AU - Li, Jun

AU - Absher, Devin

AU - Bunney, William E.

AU - Barchas, Jack D.

AU - Schatzberg, Alan F.

AU - Jones, Edward G.

AU - Meng, Fan

AU - Thompson, Robert C.

AU - Watson, Stanley J.

AU - Myers, Richard M.

AU - Akil, Huda

AU - Boehnke, Michael

AU - Chambert, Kim

AU - Moran, Jennifer

AU - Scolnick, Ed

AU - Djurovic, Srdjan

AU - Melle, Ingrid

AU - Morken, Gunnar

AU - Gill, Michael

AU - Morris, Derek

AU - Quinn, Emma

AU - Mühleisen, Thomas W.

AU - Degenhardt, Franziska A.

AU - Mattheisen, Manuel

AU - Schumacher, Johannes

AU - Maier, Wolfgang

AU - Steffens, Michael

AU - Propping, Peter

AU - Nöthen, Markus M.

AU - Anjorin, Adebayo

AU - Bass, Nick

AU - Gurling, Hugh

AU - Kandaswamy, Radhika

AU - Lawrence, Jacob

AU - McGhee, Kevin

AU - McIntosh, Andrew

AU - McLean, Alan W.

AU - Muir, Walter J.

AU - Pickard, Benjamin S.

AU - Breen, Gerome

AU - St. Clair, David

AU - Caesar, Sian

AU - Gordon-Smith, Katherine

AU - Jones, Lisa

AU - Fraser, Christine

AU - Green, Elaine K.

AU - Grozeva, Detelina

AU - Jones, Ian R.

AU - Kirov, George

AU - Moskvina, Valentina

AU - Nikolov, Ivan

AU - O'Donovan, Michael C.

AU - Owen, Michael J.

AU - Collier, David A.

AU - Elkin, Amanda

AU - Williamson, Richard

AU - Young, Allan H.

AU - Nicol Ferrier, I.

AU - Stefansson, Kari

AU - Stefansson, Hreinn

AU - Porgeirsson, Porgeir

AU - Steinberg, Stacy

AU - Gustafsson, Ómar

AU - Bergen, Sarah E.

AU - Nimgaonkar, Vishwajit

AU - Hultman, Christina

AU - Landén, Mikael

AU - Lichtenstein, Paul

AU - Sullivan, Patrick

AU - Schalling, Martin

AU - Osby, Urban

AU - Backlund, Lena

AU - Frisén, Louise

AU - Langstrom, Niklas

AU - Jamain, Stéphane

AU - Leboyer, Marion

AU - Etain, Bruno

AU - Bellivier, Frank

AU - Petursson, Hannes

AU - Sigurdsson, Engilbert

AU - Müller-Mysok, Bertram

AU - Lucae, Susanne

AU - Schwarz, Markus

AU - Fullerton, Janice M.

AU - Schofield, Peter R.

AU - Martin, Nick

AU - Montgomery, Grant W.

AU - Lathrop, Mark

AU - Óskarsson, Högni

AU - Bauer, Michael

AU - Wright, Adam

AU - Mitchell, Philip B.

AU - Hautzinger, Martin

AU - Reif, Andreas

AU - Kelsoe, John R.

AU - Purcell, Shaun M.

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80053385384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053385384&partnerID=8YFLogxK

U2 - 10.1038/ng.943

DO - 10.1038/ng.943

M3 - Article

C2 - 21926972

AN - SCOPUS:80053385384

SN - 1061-4036

VL - 43

SP - 977

EP - 985

JO - Nature genetics

JF - Nature genetics

IS - 10

ER -

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

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