Evidence for association of the non-duplicated region of CHRNA7 gene with bipolar disorder but not with Schizophrenia

Psychiatr Genet. 2010 Dec;20(6):289-97. doi: 10.1097/YPG.0b013e32833a9b7a.


Objective: Biological evidence in both human and animal studies suggests α7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) as a suitable functional candidate for genetic studies in psychiatric populations. This gene maps to chromosome 15q13-14, a major linkage hotspot for schizophrenia (SCH) and bipolar disorder (BD). In this study we examine the role of CHRNA7 in influencing the risk of SCH and BD.

Methods: In the present investigation four SNPs of the non-duplicated region of CHRNA7 were genotyped: -86C/T variant, located in the 5'-upstream regulatory region; and three intronic polymorphisms (rs883473, rs6494223 and rs904952). Genetic analysis was performed on 510 patients diagnosed with SCH, 245 with BD and on 793 unrelated healthy controls.

Results: SNP analysis suggested a significant difference in -86C/T allele (P=0.025) and genotype (P=0.03) frequencies between BD and control groups, although significance was lost after correction for multiple testing. Besides, the nucleotide change (T) in rs6494223 had a protective effect against BD [odds ratio (OR)=0.70 (0.57-0.87); P=0.001]. Genotype frequencies also showed significant association (P=0.001) [CT genotype OR=0.71 (0.5-0.96); TT genotype OR=0.47 (0.29-0.77)]. Haplotypic analysis revealed a positive association of the gene with BD (global-stat=24.18, P value=0.007) with a maximum effect in the region that covered introns 3 and 4. In contrast, no evidence of risk variants was found in the analysis of the SCH sample.

Conclusion: Our data support the non-duplicated region of CHRNA7 gene as a susceptibility region for BD but not for SCH. Further genotyping of this region may help to delimit the causal polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bipolar Disorder / genetics*
  • Female
  • Gene Duplication / genetics*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Nicotinic / genetics*
  • Schizophrenia / genetics*
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, human
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor