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 & 31 others 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, Benjamin S Pickard, Katherine Gordon-Smith, Psychiatric GWAS Consortium Bipolar Disorder Working Group

Research output: Contribution to journalArticle

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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.
LanguageEnglish
Pages977-983
Number of pages7
JournalNature Genetics
Volume43
Issue number10
Early online date18 Sep 2011
DOIs
Publication statusPublished - 2011

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Genome-Wide Association Study
Bipolar Disorder
Single Nucleotide Polymorphism
Calcium Channels
Sample Size
Psychiatry
Schizophrenia
Genome

Keywords

  • large-scale
  • genome-wide association
  • analysis
  • bipolar disorder

Cite this

Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., ... 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, Pamela ; Ripke, Stephan ; Scott, Laura J ; Andreassen, Ole A ; Cichon, Sven ; Craddock, Nick ; Edenberg, Howard J ; Nurnberger, John I ; Rietschel, Marcella ; Blackwood, Douglas ; Corvin, Aiden ; Flickinger, Matthew ; Guan, Weihua ; Mattingsdal, Morten ; McQuillin, Andrew ; Kwan, Phoenix ; Wienker, Thomas F ; Daly, Mark ; Dudbridge, Frank ; Holmans, Peter A ; Lin, Danyu ; Burmeister, Margit ; Greenwood, Tiffany A ; Hamshere, Marian L ; Muglia, Pierandrea ; Smith, Erin N ; Zandi, Peter P ; 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 ; Lawson, William B ; Nwulia, Evaristus A ; Hipolito, Maria ; Coryell, William ; Rice, John ; Byerley, William ; McMahon, Francis J ; Schulze, Thomas G ; Berrettini, Wade ; Lohoff, Falk W ; Pickard, Benjamin S ; Gordon-Smith, Katherine ; Psychiatric GWAS Consortium Bipolar Disorder Working Group. / Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. In: Nature Genetics. 2011 ; Vol. 43, No. 10. pp. 977-983.
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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, Berrettini, W, Lohoff, FW, Pickard, BS, Gordon-Smith, K & 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

Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. / Sklar, Pamela; Ripke, Stephan; Scott, Laura J; Andreassen, Ole A; Cichon, Sven; Craddock, Nick; Edenberg, Howard J; Nurnberger, John I; Rietschel, Marcella; Blackwood, Douglas; Corvin, Aiden; Flickinger, Matthew; Guan, Weihua; Mattingsdal, Morten; McQuillin, Andrew; Kwan, Phoenix; Wienker, Thomas F; Daly, Mark; Dudbridge, Frank; Holmans, Peter A; Lin, Danyu; Burmeister, Margit; Greenwood, Tiffany A; Hamshere, Marian L; Muglia, Pierandrea; Smith, Erin N; Zandi, Peter P; 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; Lawson, William B; Nwulia, Evaristus A; Hipolito, Maria; Coryell, William; Rice, John; Byerley, William; McMahon, Francis J; Schulze, Thomas G; Berrettini, Wade; Lohoff, Falk W; Pickard, Benjamin S; Gordon-Smith, Katherine; Psychiatric GWAS Consortium Bipolar Disorder Working Group.

In: Nature Genetics, Vol. 43, No. 10, 2011, p. 977-983.

Research output: Contribution to journalArticle

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 - Pickard, Benjamin S

AU - Gordon-Smith, Katherine

AU - Psychiatric GWAS Consortium Bipolar Disorder Working Group

PY - 2011

Y1 - 2011

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.

KW - large-scale

KW - genome-wide association

KW - analysis

KW - bipolar disorder

U2 - 10.1038/ng.943

DO - 10.1038/ng.943

M3 - Article

VL - 43

SP - 977

EP - 983

JO - Nature Genetics

T2 - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

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