Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 159 B, Issue 4, 2012, Pages 465-475

  Van Den Bossche, Maarten J ^a,b   Strazisar, Mojca ^a,b   De Bruyne, Stephan ^c   Bervoets, Chris ^b,d   Lenaerts, An Sofie ^a,b   De Zutter, Sonia ^a,b   Nordin, Annelie ^e   Norrback, Karl Fredrik ^e   Goossens, Dirk ^a,b   De Rijk, Peter ^a,b   Green, Elaine K ^f   Grozeva, Detelina ^f   Mendlewicz, Julien ^g   Craddock, Nick ^f   Sabbe, Bernard G ^b,h   Adolfsson, Rolf ^e   Souery, Daniel ^g,i   Del Favero, Jurgen ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b UNIVERSITY OF ANTWERP   (Belgium)

^c Psychiatric Residential Care Home Schorshaegen   (Belgium)

^d Psychiatric Hospital OLV   (Belgium)

^e UMEÅ UNIVERSITY   (Sweden)

^f CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

^g UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

^h Psychiatric Hospital Sint Norbertus   (Belgium)

ⁱ Centre Européen de Psychologie Médicale PSY PLURIEL   (Belgium)

Author keywords

Bipolar disorder; Copy number variation; Schizoaffective disorder; Schizophrenia; Voltage dependent calcium channel genes

Indexed keywords

CACNA2D4 PROTEIN; PROTEIN; UNCLASSIFIED DRUG; VOLTAGE GATED CALCIUM CHANNEL;

ARTICLE; BIPOLAR DISORDER; CONTROLLED STUDY; COPY NUMBER VARIATION; FEMALE; GENETIC SUSCEPTIBILITY; HUMAN; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA;

ADULT; AGE OF ONSET; BASE PAIRING; BELGIUM; BIPOLAR DISORDER; CALCIUM CHANNELS, L-TYPE; CHROMOSOMES, HUMAN, PAIR 12; FEMALE; GENE DELETION; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; MIDDLE AGED; PSYCHOTIC DISORDERS; SWEDEN;

EID: 84860625277     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.32053     Document Type: Article

References (85)

1. Abdelmoity AT, Hall JJ, Bittel DC, Yu S. 2011. 1.39Mb inherited interstitial deletion in 12p13.33 associated with developmental delay. Eur J Med Genet 54: 198-203.
2. Anantharaman V, Aravind L. 2000. Cache-A signaling domain common to animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors. Trends Biochem Sci 25: 535-537.
3. Bangalore R, Mehrke G, Gingrich K, Hofmann F, Kass RS. 1996. Influence of L-type Ca channel alpha 2/delta-subunit on ionic and gating current in transiently transfected HEK 293 cells. Am J Physiol 270: H1521-H1528.
4. Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nothen MM, Georgi A, Schumacher J, Schwarz M, Abou JR, Hofels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, McMahon FJ. 2008. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 13: 197-207.
5. Berridge MJ, Bootman MD, Roderick HL. 2003. Calcium signalling: Dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4: 517-529.
6. Bigos KL, Mattay VS, Callicott JH, Straub RE, Vakkalanka R, Kolachana B, Hyde TM, Lipska BK, Kleinman JE, Weinberger DR. 2010. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 67: 939-945.
7. Buizer-Voskamp JE, Muntjewerff JW, Strengman E, Sabatti C, Stefansson H, Vorstman JA, Ophoff RA. 2011. Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients. Biol Psychiatry 70: 655-662.
8. Carafoli E. 2002. Calcium signaling: A tale for all seasons. Proc Natl Acad Sci USA 99: 1115-1122.
9. Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ, Venturi P, Jones LA, Lewis SW, Sham PC, Gottesman II, Farmer AE, McGuffin P, Reveley AM, Murray RM. 1999. Heritability estimates for psychotic disorders: The Maudsley twin psychosis series. Arch Gen Psychiatry 56: 162-168.
10. Carman JS, Wyatt RJ. 1979. Calcium: Bivalent cation in the bivalent psychoses. Biol Psychiatry 14: 295-336.
11. Casamassima F, Hay AC, Benedetti A, Lattanzi L, Cassano GB, Perlis RH. 2010. L-type calcium channels and psychiatric disorders: A brief review. Am J Med Genet Part B 153B: 1373-1390.
12. Cichon S, Muhleisen TW, Degenhardt FA, Mattheisen M, Miro X, Strohmaier J, Steffens M, Meesters C, Herms S, Weingarten M, Priebe L, Haenisch B, Alexander M, Vollmer J, Breuer R, Schmal C, Tessmann P, Moebus S, Wichmann HE, Schreiber S, Muller-Myhsok B, Lucae S, Jamain S, Leboyer M, Bellivier F, Etain B, Henry C, Kahn JP, Heath S, Hamshere M, O'Donovan MC, Owen MJ, Craddock N, Schwarz M, Vedder H, Kammerer-Ciernioch J, Reif A, Sasse J, Bauer M, Hautzinger M, Wright A, Mitchell PB, Schofield PR, Montgomery GW, Medland SE, Gordon SD, Martin NG, Gustafsson O, Andreassen O, Djurovic S, Sigurdsson E, Steinberg S, Stefansson H, Stefansson K, Kapur-Pojskic L, Oruc L, Rivas F, Mayoral F, Chuchalin A, Babadjanova G, Tiganov AS, Pantelejeva G, Abramova LI, Grigoroiu-Serbanescu M, Diaconu CC, Czerski PM, Hauser J, Zimmer A, Lathrop M, Schulze TG, Wienker TF, Schumacher J, Maier W, Propping P, Rietschel M, Nothen MM. 2011. Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. Am J Hum Genet 88: 372-381.
13. de Smith AJ, Tsalenko A, Sampas N, Scheffer A, Yamada NA, Tsang P, Ben-Dor A, Yakhini Z, Ellis RJ, Bruhn L, Laderman S, Froguel P, Blakemore AI. 2007. Array CGH analysis of copy number variation identifies 1284 new genes variant in healthy white males: Implications for association studies of complex diseases. Hum Mol Genet 16: 2783-2794.
14. Depp CA, Jeste DV. 2004. Bipolar disorder in older adults: A critical review. Bipolar Disord 6: 343-367.
15. Djurovic S, Gustafsson O, Mattingsdal M, Athanasiu L, Bjella T, Tesli M, Agartz I, Lorentzen S, Melle I, Morken G, Andreassen OA. 2010. A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample. J Affect Disord 126: 312-316.
16. Dubovsky SL, Thomas M, Hijazi A, Murphy J. 1994. Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder. Eur Arch Psychiatry Clin Neurosci 243: 229-234.
17. Ekholm B, Ekholm A, Adolfsson R, Vares M, Osby U, Sedvall GC, Jonsson EG. 2005. Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses. Nord J Psychiatry 59: 457-464.
18. Erk S, Meyer-Lindenberg A, Schnell K, Opitz vonBC, Esslinger C, Kirsch P, Grimm O, Arnold C, Haddad L, Witt SH, Cichon S, Nothen MM, Rietschel M, Walter H. 2010. Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch Gen Psychiatry 67: 803-811.
19. Ferreira MA, 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 CD, Robinson M, Van BM, Pereira AC, Kandaswamy R, McQuillin A, Collier DA, Bass NJ, Young AH, Lawrence J, Ferrier IN, 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. Nat Genet 40: 1056-1058.
20. First MB, Spitzer RL, Gibbon M, Williams JB. 2002. Structured Clinical Interview for DSM-IVTR Axis I Disorders, Research Version, Patient Edition (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute.
21. Franke B, Vasquez AA, Veltman JA, Brunner HG, Rijpkema M, Fernandez G. 2010. Genetic variation in CACNA1C, a gene associated with bipolar disorder, influences brainstem rather than gray matter volume in healthy individuals. Biol Psychiatry 68: 586-588.
22. Ghosh A, Greenberg ME. 1995. Calcium signaling in neurons: Molecular mechanisms and cellular consequences. Science 268: 239-247.
23. Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, Itsara A, Vives L, Walsh T, McCarthy SE, Baker C, Mefford HC, Kidd JM, Browning SR, Browning BL, Dickel DE, Levy DL, Ballif BC, Platky K, Farber DM, Gowans GC, Wetherbee JJ, Asamoah A, Weaver DD, Mark PR, Dickerson J, Garg BP, Ellingwood SA, Smith R, Banks VC, Smith W, McDonald MT, Hoo JJ, French BN, Hudson C, Johnson JP, Ozmore JR, Moeschler JB, Surti U, Escobar LF, El-Khechen D, Gorski JL, Kussmann J, Salbert B, Lacassie Y, Biser A, McDonald-McGinn DM, Zackai EH, Deardorff MA, Shaikh TH, Haan E, Friend KL, Fichera M, Romano C, Gecz J, Delisi LE, Sebat J, King MC, Shaffer LG, Eichler EE. 2010. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet 42: 203-209.
24. Goodnick PJ. 2000. The use of nimodipine in the treatment of mood disorders. Bipolar Disord 2: 165-173.
25. Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N. 2010. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry 15: 1016-1022.
26. Grozeva D, Kirov G, Ivanov D, Jones IR, Jones L, Green EK, St Clair DM, Young AH, Ferrier N, Farmer AE, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N. 2010. Rare copy number variants: A point of rarity in genetic risk for bipolar disorder and schizophrenia. Arch Gen Psychiatry 67: 318-327.
27. International Schizophrenia Consortium. 2008. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455: 237-241.
28. Jogia J, Ruberto G, Lelli-Chiesa G, Vassos E, Maieru M, Tatarelli R, Girardi P, Collier D, Frangou S. 2011. The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder. Mol Psychiatry 16: 1070-1071.
29. Kirov G, Grozeva D, Norton N, Ivanov D, Mantripragada KK, Holmans P, Craddock N, Owen MJ, O'Donovan MC. 2009. Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Hum Mol Genet 18: 1497-1503.
30. Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M, Ruderfer D, Moran J, Chambert K, Toncheva D, Georgieva L, Grozeva D, Fjodorova M, Wollerton R, Rees E, Nikolov I, van de Lagemaat LN, Bayes A, Fernandez E, Olason PI, Bottcher Y, Komiyama NH, Collins MO, Choudhary J, Stefansson K, Stefansson H, Grant SG, Purcell S, Sklar P, O'Donovan MC, Owen MJ. 2012. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry 17: 142-153.
31. Korbel JO, Urban AE, Affourtit JP, Godwin B, Grubert F, Simons JF, Kim PM, Palejev D, Carriero NJ, Du L, Taillon BE, Chen Z, Tanzer A, Saunders AC, Chi J, Yang F, Carter NP, Hurles ME, Weissman SM, Harkins TT, Gerstein MB, Egholm M, Snyder M. 2007. Paired-end mapping reveals extensive structural variation in the human genome. Science 318: 420-426.
32. Krug A, Nieratschker V, Markov V, Krach S, Jansen A, Zerres K, Eggermann T, Stocker T, Shah NJ, Treutlein J, Muhleisen TW, Kircher T. 2010. Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals. Neuroimage 49: 1831-1836.
33. Lecrubier Y, Sheehan DV, Weiller E, Amorim P, Bonora I, Harnett Sheehan K, Janavs J, Dunbar GC. 1997. The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: Reliability and validity according to the CIDI. Eur Psychiatry 12: 224-231.
34. Lee MT, Chen CH, Lee CS, Chen CC, Chong MY, Ouyang WC, Chiu NY, Chuo LJ, Chen CY, Tan HK, Lane HY, Chang TJ, Lin CH, Jou SH, Hou YM, Feng J, Lai TJ, Tung CL, Chen TJ, Chang CJ, Lung FW, Chen CK, Shiah IS, Liu CY, Teng PR, Chen KH, Shen LJ, Cheng CS, Chang TP, Li CF, Chou CH, Chen CY, Wang KH, Fann CS, Wu JY, Chen YT, Cheng AT. 2011. Genome-wide association study of bipolar I disorder in the Han Chinese population. Mol Psychiatry 16: 548-556.
35. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. 2009. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: A population-based study. Lancet 373: 234-239.
36. Liu Y, Blackwood DH, Caesar S, de Geus EJ, Farmer A, Ferreira MA, Ferrier IN, Fraser C, Gordon-Smith K, Green EK, Grozeva D, Gurling HM, Hamshere ML, Heutink P, Holmans PA, Hoogendijk WJ, Hottenga JJ, Jones L, Jones IR, Kirov G, Lin D, McGuffin P, Moskvina V, Nolen WA, Perlis RH, Posthuma D, Scolnick EM, Smit AB, Smit JH, Smoller JW, St CD, van DR, Verhage M, Willemsen G, Young AH, Zandbelt T, Boomsma DI, Craddock N, O'Donovan MC, Owen MJ, Penninx BW, Purcell S, Sklar P, Sullivan PF. 2011. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. Mol Psychiatry 16: 2-4.
37. Malhotra D, McCarthy S, Michaelson JJ, Vacic V, Burdick KE, Yoon S, Cichon S, Corvin A, Gary S, Gershon ES, Gill M, Karayiorgou M, Kelsoe JR, Krastoshevsky O, Krause V, Leibenluft E, Levy DL, Makarov V, Bhandari A, Malhotra AK, McMahon FJ, Nothen MM, Potash JB, Rietschel M, Schulze TG, Sebat J. 2011. High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron 72: 951-963.
38. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Szatmari P, Scherer SW. 2008. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82: 477-488.
39. Mattson MP, LaFerla FM, Chan SL, Leissring MA, Shepel PN, Geiger JD. 2000. Calcium signaling in the ER: Its role in neuronal plasticity and neurodegenerative disorders. Trends Neurosci 23: 222-229.
40. McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. 2003. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 60: 497-502.
41. McQuillin A, Bass N, Anjorin A, Lawrence J, Kandaswamy R, Lydall G, Moran J, Sklar P, Purcell S, Gurling H. 2011. Analysis of genetic deletions and duplications in the University College London bipolar disorder case control sample. Eur J Hum Genet 19: 588-592.
42. Nilsson LG, BΣckman L, Erngrund K, Nyberg L. 1997. The Betula prospective cohort study: Memory, health, and aging. Aging Neuropsychol Cogn 4: 1-32.
43. Nilsson LG, Adolfsson R, BΣckman L, De Frias CM, Molander B, Nyberg L. 2004. Betula: A prospective cohort study on memory, health and aging. Aging Neuropsychol Cogn 11: 134-148.
44. Nurnberger JI Jr, Blehar MC, Kaufmann CA, York-Cooler C, Simpson SG, Harkavy-Friedman J, Severe JB, Malaspina D, Reich T. 1994. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry 51: 849-859.
45. Nyegaard M, Demontis D, Foldager L, Hedemand A, Flint TJ, Sorensen KM, Andersen PS, Nordentoft M, Werge T, Pedersen CB, Hougaard DM, Mortensen PB, Mors O, Borglum AD. 2010. CACNA1C (rs1006737) is associated with schizophrenia. Mol Psychiatry 15: 119-121.
46. Pazzaglia PJ, Post RM, Ketter TA, Callahan AM, Marangell LB, Frye MA, George MS, Kimbrell TA, Leverich GS, Cora-Locatelli G, Luckenbaugh D. 1998. Nimodipine monotherapy and carbamazepine augmentation in patients with refractory recurrent affective illness. J Clin Psychopharmacol 18: 404-413.
47. Perrier E, Pompei F, Ruberto G, Vassos E, Collier D, Frangou S. 2011. Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder. Eur Psychiatry 26: 135-137.
48. Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de JM, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le CA, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van EH, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C. 2010. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466: 368-372.
49. Priebe L, Degenhardt FA, Herms S, Haenisch B, Mattheisen M, Nieratschker V, Weingarten M, Witt S, Breuer R, Paul T, Alblas M, Moebus S, Lathrop M, Leboyer M, Schreiber S, Grigoroiu-Serbanescu M, Maier W, Propping P, Rietschel M, Nothen MM, Cichon S, Muhleisen TW. 2012. Genome-wide survey implicates the influence of copy number variants (CNVs) in the development of early-onset bipolar disorder. Mol Psychiatry 17: 421-432.
50. Qin N, Olcese R, Stefani E, Birnbaumer L. 1998. Modulation of human neuronal alpha 1E-type calcium channel by alpha 2 delta-subunit. Am J Physiol 274: C1324-C1331.
51. Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR. 2002. Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit. Mol Pharmacol 62: 485-496.
52. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, Gonzalez JR, Gratacos M, Huang J, Kalaitzopoulos D, Komura D, Macdonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A, Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW, Hurles ME. 2006. Global variation in copy number in the human genome. Nature 444: 444-454.
53. Roussos P, Giakoumaki SG, Georgakopoulos A, Robakis NK, Bitsios P. 2011. The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males. Bipolar Disord 13: 250-259.
54. Rozen S, Skaletsky H. 2000. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132: 365-386.
55. Scott LJ, Muglia P, Kong XQ, Guan W, Flickinger M, Upmanyu R, Tozzi F, Li JZ, Burmeister M, Absher D, Thompson RC, Francks C, Meng F, Antoniades A, Southwick AM, Schatzberg AF, Bunney WE, Barchas JD, Jones EG, Day R, Matthews K, McGuffin P, Strauss JS, Kennedy JL, Middleton L, Roses AD, Watson SJ, Vincent JB, Myers RM, Farmer AE, Akil H, Burns DK, Boehnke M. 2009. Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. Proc Natl Acad Sci USA 106: 7501-7506.
56. Shistik E, Ivanina T, Puri T, Hosey M, Dascal N. 1995. Ca2+ current enhancement by alpha 2/delta and beta subunits in Xenopus oocytes: Contribution of changes in channel gating and alpha 1 protein level. J Physiol 489(Pt 1): 55-62.
57. Simon-Sanchez J, Scholz S, Fung HC, Matarin M, Hernandez D, Gibbs JR, Britton A, De Vrieze FW, Peckham E, Gwinn-Hardy K, Crawley A, Keen JC, Nash J, Borgaonkar D, Hardy J, Singleton A. 2007. Genome-wide SNP assay reveals structural genomic variation, extended homozygosity and cell-line induced alterations in normal individuals. Hum Mol Genet 16: 1-14.
58. Sklar P, Smoller JW, Fan J, Ferreira MA, Perlis RH, Chambert K, Nimgaonkar VL, McQueen MB, Faraone SV, Kirby A, de Bakker PI, Ogdie MN, Thase ME, Sachs GS, Todd-Brown K, Gabriel SB, Sougnez C, Gates C, Blumenstiel B, Defelice M, Ardlie KG, Franklin J, Muir WJ, McGhee KA, MacIntyre DJ, McLean A, VanBeck M, McQuillin A, Bass NJ, Robinson M, Lawrence J, Anjorin A, Curtis D, Scolnick EM, Daly MJ, Blackwood DH, Gurling HM, Purcell SM. 2008. Whole-genome association study of bipolar disorder. Mol Psychiatry 13: 558-569.
59. Sklar P, Ripke S, Scott LJ, Andreassen OA, Cichon S, Craddock N, Edenberg HJ, Nurnberger JI Jr, 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, Potash JB, Mahon PB, McInnis MG, Zollner S, Zhang P, Craig DW, Szelinger S, Barrett TB, Breuer R, Meier S, Strohmaier J, Witt SH, Tozzi F, Farmer A, McGuffin P, Strauss J, Xu W, Kennedy JL, Vincent JB, Matthews K, Day R, Ferreira MA, O'Dushlaine C, Perlis R, Raychaudhuri S, Ruderfer D, Hyoun PL, Smoller JW, Li J, Absher D, Thompson RC, Meng FG, Schatzberg AF, Bunney WE, Barchas JD, Jones EG, Watson SJ, Myers RM, Akil H, Boehnke M, Chambert K, Moran J, Scolnick E, Djurovic S, Melle I, Morken G, Gill M, Morris D, Quinn E, Muhleisen TW, Degenhardt FA, Mattheisen M, Schumacher J, Maier W, Steffens M, Propping P, Nothen MM, Anjorin A, Bass N, Gurling H, Kandaswamy R, Lawrence J, McGhee K, McIntosh A, McLean AW, Muir WJ, Pickard BS, Breen G, St CD, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Williamson R, Young AH, Ferrier IN, Stefansson K, Stefansson H, Thornorgeirsson T, Steinberg S, Gustafsson O, Bergen SE, Nimgaonkar V, Hultman C, Landen M, Lichtenstein P, Sullivan P, Schalling M, Osby U, Backlund L, Frisen L, Langstrom N, Jamain S, Leboyer M, Etain B, Bellivier F, Petursson H, Sigur SE, Muller-Mysok B, Lucae S, Schwarz M, Schofield PR, Martin N, Montgomery GW, Lathrop M, Oskarsson H, Bauer M, Wright A, Mitchell PB, Hautzinger M, Reif A, Kelsoe JR, Purcell SM. 2011. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 43: 977-983.
60. Smith EN, Bloss CS, Badner JA, Barrett T, Belmonte PL, Berrettini W, Byerley W, Coryell W, Craig D, Edenberg HJ, Eskin E, Foroud T, Gershon E, Greenwood TA, Hipolito M, Koller DL, Lawson WB, Liu C, Lohoff F, McInnis MG, McMahon FJ, Mirel DB, Murray SS, Nievergelt C, Nurnberger J, Nwulia EA, Paschall J, Potash JB, Rice J, Schulze TG, Scheftner W, Panganiban C, Zaitlen N, Zandi PP, Zollner S, Schork NJ, Kelsoe JR. 2009. Genome-wide association study of bipolar disorder in European American and African American individuals. Mol Psychiatry 14: 755-763.
61. Smith EN, Koller DL, Panganiban C, Szelinger S, Zhang P, Badner JA, Barrett TB, Berrettini WH, Bloss CS, Byerley W, Coryell W, Edenberg HJ, Foroud T, Gershon ES, Greenwood TA, Guo Y, Hipolito M, Keating BJ, Lawson WB, Liu C, Mahon PB, McInnis MG, McMahon FJ, McKinney R, Murray SS, Nievergelt CM, Nurnberger JI Jr, Nwulia EA, Potash JB, Rice J, Schulze TG, Scheftner WA, Shilling PD, Zandi PP, Zollner S, Craig DW, Schork NJ, Kelsoe JR. 2011. Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. PLoS Genet 7: e1002134.
62. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT. 2004. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119: 19-31.
63. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Moller HJ, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di FM, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Muhleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nothen MM, Peltonen L, Collier DA, St CD, Stefansson K. 2008. Large recurrent microdeletions associated with schizophrenia. Nature 455: 232-236.
64. Sullivan PF, de Geus EJ, Willemsen G, James MR, Smit JH, Zandbelt T, Arolt V, Baune BT, Blackwood D, Cichon S, Coventry WL, Domschke K, Farmer A, Fava M, Gordon SD, He Q, Heath AC, Heutink P, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hu Y, Kohli M, Lin D, Lucae S, MacIntyre DJ, Maier W, McGhee KA, McGuffin P, Montgomery GW, Muir WJ, Nolen WA, Nothen MM, Perlis RH, Pirlo K, Posthuma D, Rietschel M, Rizzu P, Schosser A, Smit AB, Smoller JW, Tzeng JY, van DR, Verhage M, Zitman FG, Martin NG, Wray NR, Boomsma DI, Penninx BW. 2009. Genome-wide association for major depressive disorder: A possible role for the presynaptic protein piccolo. Mol Psychiatry 14: 359-375.
65. Swindell SR, Plasterer TN. 1997. SEQMAN. Contig assembly. Methods Mol Biol 70: 75-89.
66. Thimm M, Kircher T, Kellermann T, Markov V, Krach S, Jansen A, Zerres K, Eggermann T, Stocker T, Shah NJ, Nothen MM, Rietschel M, Witt SH, Mathiak K, Krug A. 2011. Effects of a CACNA1C genotype on attention networks in healthy individuals. Psychol Med 41: 1551-1561.
67. Vacic V, McCarthy S, Malhotra D, Murray F, Chou HH, Peoples A, Makarov V, Yoon S, Bhandari A, Corominas R, Iakoucheva LM, Krastoshevsky O, Krause V, Larach-Walters V, Welsh DK, Craig D, Kelsoe JR, Gershon ES, Leal SM, Dell AM, Morris DW, Gill M, Corvin A, Insel PA, McClellan J, King MC, Karayiorgou M, Levy DL, Delisi LE, Sebat J. 2011. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature 471: 499-503.
68. Velinov M, Beldia G, Gu H, Tsiouris JA, Jenkins EC, Brown WT. 2008. Psychotic manifestations in a patient with mental retardation and a 6.2megabase deletion at the distal short arm of chromosome 12. CNS Spectr 13: 515-519.
69. Veltman JA, Brunner HG. 2010. Understanding variable expressivity in microdeletion syndromes. Nat Genet 42: 192-193.
70. Vrijenhoek T, Buizer-Voskamp JE, van dS I, Strengman E, Sabatti C, Geurts vanKA, Brunner HG, Ophoff RA, Veltman JA. 2008. Recurrent CNVs disrupt three candidate genes in schizophrenia patients. Am J Hum Genet 83: 504-510.
71. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J. 2008. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320: 539-543.
72. Wang F, McIntosh AM, He Y, Gelernter J, Blumberg HP. 2011. The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disord 13: 696-700.
73. Warsh JJ, Andreopoulos S, Li PP. 2004. Role of intracellular calcium signaling in the pathophysiology and pharmacotherapy of bipolar disorder: Current status. Clin Neurosci Res 4: 201-213.
74. Weckx S, Del-Favero J, Rademakers R, Claes L, Cruts M, De JP, Van BC, De RP. 2005. novoSNP, a novel computational tool for sequence variation discovery. Genome Res 15: 436-442.
75. Wellcome Trust Case Control Consortium. 2007. Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 447: 661-678.
76. Wellcome Trust Case Control Consortium. 2010. Genome-wide association study of CNVs in 16, 000 cases of eight common diseases and 3, 000 shared controls. Nature 464: 713-720.
77. Wessa M, Linke J, Witt SH, Nieratschker V, Esslinger C, Kirsch P, Grimm O, Hennerici MG, Gass A, King AV, Rietschel M. 2010. The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol Psychiatry 15: 1126-1127.
78. Wing JK, Babor T, Brugha T, Burke J, Cooper JE, Giel R, Jablenski A, Regier D, Sartorius N. 1990. SCAN. Schedules for Clinical Assessment in Neuropsychiatry. Arch Gen Psychiatry 47: 589-593.
79. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van OJ Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. 2011. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21: 655-679.
80. Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M. 2008. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet 40: 880-885.
81. Yassa R, Nair NP, Iskandar H. 1988. Late-onset bipolar disorder. Psychiatr Clin North Am 11: 117-131.
82. Zhang D, Cheng L, Qian Y, Alliey-Rodriguez N, Kelsoe JR, Greenwood T, Nievergelt C, Barrett TB, McKinney R, Schork N, Smith EN, Bloss C, Nurnberger J, Edenberg HJ, Foroud T, Sheftner W, Lawson WB, Nwulia EA, Hipolito M, Coryell W, Rice J, Byerley W, McMahon F, Schulze TG, Berrettini W, Potash JB, Belmonte PL, Zandi PP, McInnis MG, Zollner S, Craig D, Szelinger S, Koller D, Christian SL, Liu C, Gershon ES. 2009. Singleton deletions throughout the genome increase risk of bipolar disorder. Mol Psychiatry 14: 376-380.
83. Zhang Q, Shen Q, Xu Z, Chen M, Cheng L, Zhai J, Gu H, Bao X, Chen X, Wang K, Deng X, Ji F, Liu C, Li J, Dong Q, Chen C. 2012. The effects of CACNA1C gene polymorphism on spatial working memory in both healthy controls and patients with schizophrenia or bipolar disorder. Neuropsychopharmacology 37: 677-684.
84. Zogopoulos G, Ha KC, Naqib F, Moore S, Kim H, Montpetit A, Robidoux F, Laflamme P, Cotterchio M, Greenwood C, Scherer SW, Zanke B, Hudson TJ, Bader GD, Gallinger S. 2007. Germ-line DNA copy number variation frequencies in a large North American population. Hum Genet 122: 345-353.
85. Zuccotti A, Clementi S, Reinbothe T, Torrente A, Vandael DH, Pirone A. 2011. Structural and functional differences between L-type calcium channels: Crucial issues for future selective targeting. Trends Pharmacol Sci 32: 366-375.