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; Jr. Nurnberger John I.; 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 Zoellner; Peng Zhang; David W. Craig; Szabocls Szelinger; Thomas B. Barrett; Rene 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 L. Hyoun; Jordan W. Smoller; Jun Li; Devin Absher; Robert C. Thompson; Fan Guo Meng; Alan F. Schatzberg; William E. Bunney; Jack D. Barchas; Edward G. Jones; 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. Muehleisen; Franziska A. Degenhardt; Manuel Mattheisen; Gerome Breen

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, Jr. Nurnberger John I., 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 Zoellner, Peng Zhang, David W. Craig, Szabocls Szelinger, Thomas B. Barrett, Rene 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 L. Hyoun, Jordan W. Smoller, Jun Li, Devin Absher, Robert C. Thompson, Fan Guo Meng, Alan F. Schatzberg, William E. Bunney, Jack D. Barchas, Edward G. Jones, 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. Muehleisen, Franziska A. Degenhardt, Manuel Mattheisen, Gerome Breen

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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
Article number	N/A
Pages (from-to)	977-983
Number of pages	7
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.943
Publication status	Published - Oct 2011

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Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., Edenberg, H. J., Nurnberger John I., J., Rietschel, M., Blackwood, D., Corvin, A., Flickinger, M., Guan, W., Mattingsdal, M., McQuillin, A., Kwan, P., Wienker, T. F., Daly, M., Dudbridge, F., ... Breen, G. (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics, 43(10), 977-983. Article N/A. https://doi.org/10.1038/ng.943

@article{a387c18ef6bc4003b5e54da9da6b036c,

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.}, Jr. 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 Zoellner and Peng Zhang and Craig, {David W.} and Szabocls Szelinger and Barrett, {Thomas B.} and Rene 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 Hyoun, {Phil L.} and Smoller, {Jordan W.} and Jun Li and Devin Absher and Thompson, {Robert C.} and Meng, {Fan Guo} and Schatzberg, {Alan F.} and Bunney, {William E.} and Barchas, {Jack D.} and Jones, {Edward G.} 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 Muehleisen, {Thomas W.} and Degenhardt, {Franziska A.} and Manuel Mattheisen and Gerome Breen",

year = "2011",

month = oct,

doi = "10.1038/ng.943",

language = "English",

volume = "43",

pages = "977--983",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Research",

number = "10",

}

Sklar, P, Ripke, S, Scott, LJ, Andreassen, OA, Cichon, S, Craddock, N, Edenberg, HJ, Nurnberger John I., J, 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, Zoellner, 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, Hyoun, PL, Smoller, JW, Li, J, Absher, D, Thompson, RC, Meng, FG, Schatzberg, AF, Bunney, WE, Barchas, JD, Jones, EG, 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, Muehleisen, TW, Degenhardt, FA, Mattheisen, M & Breen, G 2011, 'Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4', Nature Genetics, vol. 43, no. 10, N/A, pp. 977-983. https://doi.org/10.1038/ng.943

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., Jr.

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 - Zoellner, Sebastian

AU - Zhang, Peng

AU - Craig, David W.

AU - Szelinger, Szabocls

AU - Barrett, Thomas B.

AU - Breuer, Rene

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 - Hyoun, Phil L.

AU - Smoller, Jordan W.

AU - Li, Jun

AU - Absher, Devin

AU - Thompson, Robert C.

AU - Meng, Fan Guo

AU - Schatzberg, Alan F.

AU - Bunney, William E.

AU - Barchas, Jack D.

AU - Jones, Edward G.

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 - Muehleisen, Thomas W.

AU - Degenhardt, Franziska A.

AU - Mattheisen, Manuel

AU - Breen, Gerome

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.

U2 - 10.1038/ng.943

DO - 10.1038/ng.943

M3 - Article

SN - 1546-1718

VL - 43

SP - 977

EP - 983

JO - Nature Genetics

JF - Nature Genetics

IS - 10

M1 - N/A

ER -

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

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