Association analysis of CHMP1.5 genetic variation and bipolar disorder

Objectives: The 18p11.2 region surrounding the G-olf gene has been linked in several independent studies to bipolar disorder and schizophrenia, yet association studies between G-olf genetic variations and bipolar disorder have been negative. We hypothesized that the linkage in this region might be due to a gene in close physical proximity to G-olf, and we examined variations in the CHMP1.5 gene within intron 5 of G-olf for association with bipolar disorder. Methods: Two single-nucleotide polymorphisms, rs1786581 and rs1249624, were analyzed for association with bipolar disorder in 402 unrelated bipolar individuals and 181 unrelated controls. Genotyping was performed via pyrosequencing and restriction fragment length polymorphism analysis; results were compared by χ² contingency analysis. Results: No evidence was found for association of either allele at rs1249624 with bipolar disorder (χ² = 1.25, degrees of freedom = 1, P = 0.26); however, a trend towards association with the T allele at rs1786581 and with the 'T/T' 1786581/1249624 haplotype was observed. The χ² for the haplotype was 7.16, (degrees of freedom = 3, P = 0.067) and for rs1786581 χ² = 3.56, degrees of freedom = 1, P = 0.060; these differences are not statistically significant. Conclusions: Variation in the CHMP1.5 gene does not appear to be associated with bipolar disorder. A systematic assessment of genetic variation in the region using association studies will be necessary.