No association between common variations in the neuronal nicotinic acetylcholine receptor alpha2 subunit gene (CHRNA2) and bipolar I disorder

The neuronal nicotinic acetylcholine receptor alpha2 subunit gene (CHRNA2) maps to the bipolar susceptibility locus on chromosome 8p21-22. Given the biological role of the neuronal nicotinic acetylcholine receptors and the substantial comorbidity of nicotine dependence in psychiatric disorders, the CHRNA2 gene is a plausible candidate gene for bipolar disorder (BPD). We tested the hypothesis that variations in the CHRNA2 gene confer susceptibility to bipolar I disorder in a case-control association study. Genotypes of one amino acid substitution polymorphism (Ala125Thr) and five non-coding variations across the CHRNA2 gene were obtained from 345 unrelated bipolar I patients and 273 control samples. Genotypes and allele frequencies were compared between groups using chi-square contingency analysis. Linkage disequilibrium (LD) between markers was calculated, and estimated haplotype frequencies were compared between groups. We observed no statitistically significant difference in genotype and allele frequencies for all six variations between bipolar patients and controls, but we did demonstrate strong LD throughout the gene. Haplotype analysis showed that no combinations of alleles were associated with illness. Our results suggest that common variations in the CHRNA2 gene are unlikely to confer susceptibility to BPD in this sample. Further studies are required to elucidate the susceptibility locus for BPD on chromosome 8p21-22.