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; Jun Li; Gerome Breen; David St Clair; Psychiatric GWAS Consortium Bipolar Disorder Working Group

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, Jun Li, Gerome Breen, David St Clair, Psychiatric GWAS Consortium Bipolar Disorder Working Group

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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
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

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., ... Psychiatric GWAS Consortium Bipolar Disorder Working Group (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

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, Li, J, Breen, G, St Clair, D & Psychiatric GWAS Consortium Bipolar Disorder Working Group 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

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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.",

keywords = "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",

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 Jun Li and Gerome Breen and {St Clair}, David and {Psychiatric GWAS Consortium Bipolar Disorder Working Group}",

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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 - Li, Jun

AU - Breen, Gerome

AU - St Clair, David

AU - Psychiatric GWAS Consortium Bipolar Disorder Working Group

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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.

KW - alleles

KW - bipolar disorder

KW - calcium channels, L-type

KW - case-control studies

KW - databases, genetic

KW - genetic loci

KW - genetic predisposition to disease

KW - genome, human

KW - genome-wide association study

KW - humans

KW - linkage disequilibrium

KW - nuclear proteins

KW - polymorphism, single nucleotide

KW - schizophrenia

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DO - 10.1038/ng.943

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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

UN SDGs

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