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

被引:905
作者
Ferreira, Manuel A. R. [1 ,2 ,3 ,4 ,5 ,6 ]
O'Donovan, Michael C. [7 ]
Meng, Yan A. [1 ,2 ,3 ,4 ,5 ]
Jones, Ian R. [7 ]
Ruderfer, Douglas M. [1 ,3 ,4 ,5 ]
Jones, Lisa [8 ]
Fan, Jinbo [1 ,3 ,4 ,5 ]
Kirov, George [7 ]
Perlis, Roy H. [1 ,3 ,4 ,5 ]
Green, Elaine K. [7 ]
Smoller, Jordan W. [2 ,4 ,5 ]
Grozeva, Detelina [7 ]
Stone, Jennifer [1 ,2 ,3 ,4 ,5 ]
Nikolov, Ivan [7 ,9 ]
Chambert, Kimberly [4 ,5 ]
Hamshere, Marian L. [7 ,9 ]
Nimgaonkar, Vishwajit L. [10 ]
Moskvina, Valentina [7 ,9 ]
Thase, Michael E. [11 ,12 ]
Caesar, Sian [8 ]
Sachs, Gary S. [1 ,2 ]
Franklin, Jennifer
Gordon-Smith, Katherine [8 ]
Ardlie, Kristin G. [4 ,5 ]
Gabriel, Stacey B. [4 ,5 ]
Fraser, Christine [7 ]
Blumenstiel, Brendan [4 ,5 ]
Defelice, Matthew [4 ,5 ]
Breen, Gerome [13 ,14 ]
Gill, Michael [15 ]
Morris, Derek W. [15 ]
Elkin, Amanda [14 ]
Muir, Walter J. [16 ]
McGhee, Kevin A. [16 ]
Williamson, Richard [14 ]
MacIntyre, Donald J. [16 ]
MacLean, Alan W. [16 ]
Clair, David St [13 ]
Robinson, Michelle [17 ]
Van Beck, Margaret [16 ]
Pereira, Ana C. P. [17 ]
Kandaswamy, Radhika [17 ]
McQuillin, Andrew [17 ]
Collier, David A. [14 ]
Bass, Nicholas J. [17 ]
Young, Allan H. [18 ,19 ]
Lawrence, Jacob [17 ]
Ferrier, I. Nicol [18 ]
Anjorin, Adebayo [17 ]
Farmer, Anne
机构
[1] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA
[4] Harvard Univ, Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA 02142 USA
[5] MIT, Cambridge, MA 02142 USA
[6] Queensland Inst Med Res, Brisbane, Qld 4029, Australia
[7] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, England
[8] Univ Birmingham, Div Neurosci, Dept Psychiat, Birmingham B15 2QZ, England
[9] Cardiff Univ, Sch Med, Biostat & Bioinformat Unit, Cardiff CF14 4XN, England
[10] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA
[11] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
[12] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA
[13] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
[14] Kings Coll London, Inst Psychiat, SGDP, London SE5 8AF, England
[15] St James Hosp, Trinity Coll, Trinity Ctr hlth Sci, Dublin 8, Ireland
[16] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland
[17] UCL, Windeyer Inst Med Sci, Dept Mental Hlth Sci, Mol Psychiat Lab, London W1T 4JF, England
[18] Royal Victoria Infirm, Sch Neurol Neurolbiol & Psychiat, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
[19] UBC, Inst Mental Hlth, Vancouver, BC V6T 2A1, Canada
[20] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[21] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[22] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA
[23] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
基金
英国医学研究理事会; 爱尔兰科学基金会; 英国惠康基金;
关键词
D O I
10.1038/ng.209
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 x 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 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.
引用
收藏
页码:1056 / 1058
页数:3
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