Mapping of hKCa3 to chromosome 1q21 and investigation of linkage of CAG repeat polymorphism to schizophrenia

CAG trinucleotide polymorphisms in the neuronal small conductance calcium-activated potassium channel gene hKCa3 have been reported to be associated with schizophrenia. Attempts to confirm this finding have met with mixed results. We investigated hKCa3 CAG allele lengths in families from the National Institute of Mental Health (NIMH) Schizophrenia Genetics Initiative, by comparing transmission to discordant siblings and parental transmission to affected offspring. Overall, there was no convincing evidence that hKCa3 CAG lengths differ between schizophrenics and controls. We did, however, observe a trend (P = 0.063) toward over-representation of long (greater than or equal to 19) CAG repeats in the shorter of the two hKCa3 alleles in schizophrenics. There was no evidence of excessive parental transmission of long CAG repeat alleles to affected offspring. In addition, we re-mapped hKCa3 and found that it resides on chromosome 1q21, in a region which has been linked to familial hemiplegic migraine, but not to schizophrenia. These data provide no significant support for the association of hKCa3 with schizophrenia.