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; Keith Matthews; Jennifer Moran; Andrew McIntosh; Psychiat GWAS Consortium Bipolar D

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, Keith Matthews, Jennifer Moran, Andrew McIntosh, Psychiat GWAS Consortium Bipolar D

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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.

Original language	English
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

Keywords

PSYCHIATRIC-DISORDERS
SCHIZOPHRENIA
INDIVIDUALS
CACNA1C
RISK
PSYCHOSIS
GENETICS
ANK3

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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., ... Psychiat GWAS Consortium Bipolar D (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics, 43(10), 977-983. https://doi.org/10.1038/ng.943

@article{9e956169850d4ad787817cad0250b1cc,

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 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.",

keywords = "PSYCHIATRIC-DISORDERS, SCHIZOPHRENIA, INDIVIDUALS, CACNA1C, RISK, PSYCHOSIS, GENETICS, ANK3",

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 Keith Matthews and Jennifer Moran and Andrew McIntosh and {Psychiat GWAS Consortium Bipolar D}",

year = "2011",

month = oct,

doi = "10.1038/ng.943",

language = "English",

volume = "43",

pages = "977--983",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

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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, Matthews, K, Moran, J, McIntosh, A & Psychiat GWAS Consortium Bipolar D 2011, 'Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4', Nature Genetics, vol. 43, no. 10, pp. 977-983. 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.

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 - Matthews, Keith

AU - Moran, Jennifer

AU - McIntosh, Andrew

AU - Psychiat GWAS Consortium Bipolar D

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 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.

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 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.

KW - PSYCHIATRIC-DISORDERS

KW - SCHIZOPHRENIA

KW - INDIVIDUALS

KW - CACNA1C

KW - RISK

KW - PSYCHOSIS

KW - GENETICS

KW - ANK3

U2 - 10.1038/ng.943

DO - 10.1038/ng.943

M3 - Article

C2 - 21926972

SN - 1061-4036

VL - 43

SP - 977

EP - 983

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

Abstract

Keywords

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