Genetic polymorphism at the CLOCK gene locus and major depression

Genetic analysis in both mouse and Drosophila has indicated that the produc t of the CLOCK gene is an essential component of a circadian rhythm timing system. A single nucleotide polymorphism (SNP), T3111C, in the 3' flanking region of the human CLOCK gene has been identified. Homozygotes or heterozy gotes for the 3111C allele have been reported to have higher mean scores on a measure of evening preference for activity (Vs, morning preference) than subjects homozygous for the 3111T allele, Since major depression is hypoth esized to be closely linked to circadian rhythms, we explored whether this polymorphism might be related to susceptibility to major depression. We als o ascertained allele frequency in an African-American control population, t o begin to evaluate population variation at this locus. CLOCK T3111C allele frequencies were determined in 280 European American (EA) subjects, 143 wi th a history of major depression and 137 screened controls, and in 58 Afric an American (AA) screened control subjects, using a polymerase chain reacti on (PCR) - restriction fragment length polymorphism (RFLP) method. There wa s no significant difference between EA depressed and control subjects in al lele frequency. There was a significant difference in allele frequency betw een EA and AA subjects, demonstrating a potential for population stratifica tion. In none of these groups were significant deviations from Hardy-Weinbe rg equilibrium found. The present data do not support an association betwee n CLOCK gene alleles at the T3111C locus and major depression. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:418-421, 2000. Published 2000 Wiley-Liss , Inc.dagger