Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

Manuel A.R. Ferreira; Michael C. O'Donovan; Yan A. Meng; Ian R. Jones; Douglas M. Ruderfer; Lisa Jones; Jinbo Fan; George Kirov; Roy H. Perlis; Elaine K. Green; Jordan W. Smoller; Detelina Grozeva; Jennifer Stone; Ivan Nikolov; Kimberly Chambert; Marian L. Hamshere; Vishwajit L. Nimgaonkar; Valentina Moskvina; Michael E. Thase; Sian Caesar; Gary S. Sachs; Jennifer Franklin; Katherine Gordon-Smith; Kristin G. Ardlie; Stacey B. Gabriel; Christine Fraser; Brendan Blumenstiel; Matthew Defelice; Gerome Breen; Michael Gill; Derek W. Morris; Amanda Elkin; Walter J. Muir; Kevin A. McGhee; Richard Williamson; Donald J. MacIntyre; Alan W. MacLean; David St Clair; Michelle Robinson; Margaret Van Beck; Ana C.P. Pereira; Radhika Kandaswamy; Andrew McQuillin; David A. Collier; Nicholas J. Bass; Allan H. Young; Jacob Lawrence; I. Nicol Ferrier; Adebayo Anjorin; Anne Farmer; David Curtis; Edward M. Scolnick; Peter McGuffin; Mark J. Daly; Aiden P. Corvin; Peter A. Holmans; Douglas H. Blackwood; Hugh M. Gurling; Michael J. Owen; Shaun M. Purcell; Pamela Sklar; Nick Craddock

doi:10.1038/ng.209

Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

Manuel A.R. Ferreira, Michael C. O'Donovan, Yan A. Meng, Ian R. Jones, Douglas M. Ruderfer, Lisa Jones, Jinbo Fan, George Kirov, Roy H. Perlis, Elaine K. Green, Jordan W. Smoller, Detelina Grozeva, Jennifer Stone, Ivan Nikolov, Kimberly Chambert, Marian L. Hamshere, Vishwajit L. Nimgaonkar, Valentina Moskvina, Michael E. Thase, Sian CaesarGary S. Sachs, Jennifer Franklin, Katherine Gordon-Smith, Kristin G. Ardlie, Stacey B. Gabriel, Christine Fraser, Brendan Blumenstiel, Matthew Defelice, Gerome Breen, Michael Gill, Derek W. Morris, Amanda Elkin, Walter J. Muir, Kevin A. McGhee, Richard Williamson, Donald J. MacIntyre, Alan W. MacLean, David St Clair, Michelle Robinson, Margaret Van Beck, Ana C.P. Pereira, Radhika Kandaswamy, Andrew McQuillin, David A. Collier, Nicholas J. Bass, Allan H. Young, Jacob Lawrence, I. Nicol Ferrier, Adebayo Anjorin, Anne Farmer, David Curtis, Edward M. Scolnick, Peter McGuffin, Mark J. Daly, Aiden P. Corvin, Peter A. Holmans, Douglas H. Blackwood, Hugh M. Gurling, Michael J. Owen, Shaun M. Purcell, Pamela Sklar, Nick Craddock

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Abstract

To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 × 10^-9) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 × 10^-8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.

Original language	English
Pages (from-to)	1056-1058
Number of pages	3
Journal	Nature Genetics
Volume	40
Issue number	9
DOIs	https://doi.org/10.1038/ng.209
State	Published - Sep 2008
Externally published	Yes

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Ferreira, M. A. R., O'Donovan, M. C., Meng, Y. A., Jones, I. R., Ruderfer, D. M., Jones, L., Fan, J., Kirov, G., Perlis, R. H., Green, E. K., Smoller, J. W., Grozeva, D., Stone, J., Nikolov, I., Chambert, K., Hamshere, M. L., Nimgaonkar, V. L., Moskvina, V., Thase, M. E., ... Craddock, N. (2008). Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nature Genetics, 40(9), 1056-1058. https://doi.org/10.1038/ng.209

@article{e15a581572454cad94fe6558ce1545cd,

title = "Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder",

abstract = "To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 × 10-9) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 × 10-8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.",

author = "Ferreira, {Manuel A.R.} and O'Donovan, {Michael C.} and Meng, {Yan A.} and Jones, {Ian R.} and Ruderfer, {Douglas M.} and Lisa Jones and Jinbo Fan and George Kirov and Perlis, {Roy H.} and Green, {Elaine K.} and Smoller, {Jordan W.} and Detelina Grozeva and Jennifer Stone and Ivan Nikolov and Kimberly Chambert and Hamshere, {Marian L.} and Nimgaonkar, {Vishwajit L.} and Valentina Moskvina and Thase, {Michael E.} and Sian Caesar and Sachs, {Gary S.} and Jennifer Franklin and Katherine Gordon-Smith and Ardlie, {Kristin G.} and Gabriel, {Stacey B.} and Christine Fraser and Brendan Blumenstiel and Matthew Defelice and Gerome Breen and Michael Gill and Morris, {Derek W.} and Amanda Elkin and Muir, {Walter J.} and McGhee, {Kevin A.} and Richard Williamson and MacIntyre, {Donald J.} and MacLean, {Alan W.} and {St Clair}, David and Michelle Robinson and {Van Beck}, Margaret and Pereira, {Ana C.P.} and Radhika Kandaswamy and Andrew McQuillin and Collier, {David A.} and Bass, {Nicholas J.} and Young, {Allan H.} and Jacob Lawrence and {Nicol Ferrier}, I. and Adebayo Anjorin and Anne Farmer and David Curtis and Scolnick, {Edward M.} and Peter McGuffin and Daly, {Mark J.} and Corvin, {Aiden P.} and Holmans, {Peter A.} and Blackwood, {Douglas H.} and Gurling, {Hugh M.} and Owen, {Michael J.} and Purcell, {Shaun M.} and Pamela Sklar and Nick Craddock",

note = "Funding Information: Study supported by US National Institute of Mental Health (MH062137, MH067288, P.S.; MH063445, J.W.S.; MH63420, V.L.N.; N01MH80001, G.S.S., M.E.T. and M.S. Bauer), NARSAD (R.H.P., S.P., J.F., P.S.); Johnson & Johnson Pharmaceutical Research & Development, Sylvan C. Herman Foundation, Stanley Medical Research Institute, Dauten Family, Merck Genome Research Institute (E.M.S.); and National Health Medical Research Council (MRC), Australia (M.A.R.F.). Broad Institute Center for Genotyping and Analysis supported by U54 RR020278, National Center for Research Resources. UCL sample collection supported by MDF–The Bipolar Organization, Neuroscience Research Charitable Trust, central London NHS Blood Transfusion Service, Priory Hospitals and UK MRC (G9623693N, G0500791). Dublin sample collection supported by the Health Research Board and Science Foundation Ireland; controls supplied by J. McPartlin, Trinity College Biobank. Edinburgh cohort collection supported by the Wellcome Trust, London, Chief Scientist Office of the Scottish Executive and MRC, London. WTCCC genotype analyses were funded by the Wellcome Trust and undertaken within the context of the WTCCC. WTCCC members are listed in Supplementary Note.",

year = "2008",

month = sep,

doi = "10.1038/ng.209",

language = "English",

volume = "40",

pages = "1056--1058",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "9",

}

Ferreira, MAR, O'Donovan, MC, Meng, YA, Jones, IR, Ruderfer, DM, Jones, L, Fan, J, Kirov, G, Perlis, RH, Green, EK, Smoller, JW, Grozeva, D, Stone, J, Nikolov, I, Chambert, K, Hamshere, ML, Nimgaonkar, VL, Moskvina, V, Thase, ME, Caesar, S, Sachs, GS, Franklin, J, Gordon-Smith, K, Ardlie, KG, Gabriel, SB, Fraser, C, Blumenstiel, B, Defelice, M, Breen, G, Gill, M, Morris, DW, Elkin, A, Muir, WJ, McGhee, KA, Williamson, R, MacIntyre, DJ, MacLean, AW, St Clair, D, Robinson, M, Van Beck, M, Pereira, ACP, Kandaswamy, R, McQuillin, A, Collier, DA, Bass, NJ, Young, AH, Lawrence, J, Nicol Ferrier, I, Anjorin, A, Farmer, A, Curtis, D, Scolnick, EM, McGuffin, P, Daly, MJ, Corvin, AP, Holmans, PA, Blackwood, DH, Gurling, HM, Owen, MJ, Purcell, SM, Sklar, P & Craddock, N 2008, 'Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder', Nature Genetics, vol. 40, no. 9, pp. 1056-1058. https://doi.org/10.1038/ng.209

TY - JOUR

T1 - Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

AU - Ferreira, Manuel A.R.

AU - O'Donovan, Michael C.

AU - Meng, Yan A.

AU - Jones, Ian R.

AU - Ruderfer, Douglas M.

AU - Jones, Lisa

AU - Fan, Jinbo

AU - Kirov, George

AU - Perlis, Roy H.

AU - Green, Elaine K.

AU - Smoller, Jordan W.

AU - Grozeva, Detelina

AU - Stone, Jennifer

AU - Nikolov, Ivan

AU - Chambert, Kimberly

AU - Hamshere, Marian L.

AU - Nimgaonkar, Vishwajit L.

AU - Moskvina, Valentina

AU - Thase, Michael E.

AU - Caesar, Sian

AU - Sachs, Gary S.

AU - Franklin, Jennifer

AU - Gordon-Smith, Katherine

AU - Ardlie, Kristin G.

AU - Gabriel, Stacey B.

AU - Fraser, Christine

AU - Blumenstiel, Brendan

AU - Defelice, Matthew

AU - Breen, Gerome

AU - Gill, Michael

AU - Morris, Derek W.

AU - Elkin, Amanda

AU - Muir, Walter J.

AU - McGhee, Kevin A.

AU - Williamson, Richard

AU - MacIntyre, Donald J.

AU - MacLean, Alan W.

AU - St Clair, David

AU - Robinson, Michelle

AU - Van Beck, Margaret

AU - Pereira, Ana C.P.

AU - Kandaswamy, Radhika

AU - McQuillin, Andrew

AU - Collier, David A.

AU - Bass, Nicholas J.

AU - Young, Allan H.

AU - Lawrence, Jacob

AU - Nicol Ferrier, I.

AU - Anjorin, Adebayo

AU - Farmer, Anne

AU - Curtis, David

AU - Scolnick, Edward M.

AU - McGuffin, Peter

AU - Daly, Mark J.

AU - Corvin, Aiden P.

AU - Holmans, Peter A.

AU - Blackwood, Douglas H.

AU - Gurling, Hugh M.

AU - Owen, Michael J.

AU - Purcell, Shaun M.

AU - Sklar, Pamela

AU - Craddock, Nick

N1 - Funding Information: Study supported by US National Institute of Mental Health (MH062137, MH067288, P.S.; MH063445, J.W.S.; MH63420, V.L.N.; N01MH80001, G.S.S., M.E.T. and M.S. Bauer), NARSAD (R.H.P., S.P., J.F., P.S.); Johnson & Johnson Pharmaceutical Research & Development, Sylvan C. Herman Foundation, Stanley Medical Research Institute, Dauten Family, Merck Genome Research Institute (E.M.S.); and National Health Medical Research Council (MRC), Australia (M.A.R.F.). Broad Institute Center for Genotyping and Analysis supported by U54 RR020278, National Center for Research Resources. UCL sample collection supported by MDF–The Bipolar Organization, Neuroscience Research Charitable Trust, central London NHS Blood Transfusion Service, Priory Hospitals and UK MRC (G9623693N, G0500791). Dublin sample collection supported by the Health Research Board and Science Foundation Ireland; controls supplied by J. McPartlin, Trinity College Biobank. Edinburgh cohort collection supported by the Wellcome Trust, London, Chief Scientist Office of the Scottish Executive and MRC, London. WTCCC genotype analyses were funded by the Wellcome Trust and undertaken within the context of the WTCCC. WTCCC members are listed in Supplementary Note.

PY - 2008/9

Y1 - 2008/9

N2 - To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 × 10-9) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 × 10-8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.

AB - To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 × 10-9) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 × 10-8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.

UR - http://www.scopus.com/inward/record.url?scp=50449089356&partnerID=8YFLogxK

U2 - 10.1038/ng.209

DO - 10.1038/ng.209

M3 - Article

C2 - 18711365

AN - SCOPUS:50449089356

SN - 1061-4036

VL - 40

SP - 1056

EP - 1058

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

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