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 factor common to both diseases. Genetic loci may also be detected which influence which of the two diseases occurs if common risk factors are present.
We used samples of UK bipolar and schizophrenic cases which had previously 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.
Eight markers were significant at p<10−5. Of these, the most interesting finding was for rs17645023 which was significant at p<10−6 and which lies 36kb from CACNG5. Control allele frequencies for this marker were intermediate between those for bipolar and schizophrenic cases.
Application of this approach suggests that it does have some merits. The finding for CACNG5, taken together with the prior 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.
Keywords: Schizophrenia, bipolar disorder, association, calcium channel