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Case–case genome-wide association analysis shows markers differentially associated with schizophrenia and bipolar disorder and implicates calcium channel genes

Curtis, Davida; Vine, Anna E.a; McQuillin, Andrewb; Bass, Nicholas Jamesb; Pereira, Anab; Kandaswamy, Radhikab; Lawrence, Jacobb; Anjorin, Adebayob; Choudhury, Khalidb; Datta, Susmita R.b; Puri, Vinayb; Krasucki, Robertb; Pimm, Jonathanb; Thirumalai, Srinivasab; Quested, Digbyb; Gurling, Hugh M.D.b

doi: 10.1097/YPG.0b013e3283413382
Original Articles

Objective There are theoretical reasons why comparing marker allele frequencies between cases of different diseases, rather than with controls, may offer benefits. The samples may be better matched, especially for background risk factors common to both diseases. Genetic loci may also be detected which influence which of the two diseases occurs if common risk factors are present.

Method We used samples of UK bipolar and schizophrenic cases that had earlier been subject to genome-wide association studies and compared marker allele frequencies between the two samples. When these differed for a marker, we compared the case sample allele frequencies with those of a control sample.

Results Eight markers were significant at P value of less than 10−5. Of these, the most interesting finding was for rs17645023, which was significant at P value of less than 10−6 and which lies 36 kb from CACNG5. Control allele frequencies for this marker were intermediate between those for bipolar and schizophrenic cases.

Conclusion The application of this approach suggests that it does have some merits. The finding for CACNG5, taken together with the earlier implication of CACNA1C and CACNA1B, strongly suggests a key role for voltage-dependent calcium channel genes in the susceptibility to bipolar disorder and/or schizophrenia.

aCentre for Psychiatry, Barts and the London School of Medicine and Dentistry

bDepartment of Mental Health Sciences, Molecular Psychiatry Laboratory, Windeyer Institute of Medical Sciences, University College London, London, UK

Correspondence to Professor David Curtis, MD, PhD, Adult Psychiatry, Royal London Hospital, London E11BB, UK Tel: +44 207 3777729; fax: +44 207 3777316; e-mail:

Received December 23, 2009

Accepted May 8, 2010

© 2011 Lippincott Williams & Wilkins, Inc.