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-a ctivated potassium channel gene hKCa3 have been reported to be associated w ith schizophrenia. Attempts to confirm this finding have met with mixed res ults. We investigated hKCa3 CAG allele lengths in families from the Nationa l Institute of Mental Health (NIMH) Schizophrenia Genetics Initiative, by c omparing transmission to discordant siblings and parental transmission to a ffected offspring. Overall, there was no convincing evidence that hKCa3 CAG lengths differ between schizophrenics and controls. We did, however, obser ve 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 schizop hrenics. There was no evidence of excessive parental transmission of long C AG repeat alleles to affected offspring. In addition, we re-mapped hKCa3 an d found that it resides on chromosome 1q21, in a region which has been link ed to familial hemiplegic migraine, but not to schizophrenia. These data pr ovide no significant support for the association of hKCa3 with schizophreni a.