Psychiatric Genetics

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Psychiatric Genetics:
doi: 10.1097/YPG.0b013e32833a9b7a
Original Articles

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

Ancín, Inésa; Barabash, Anaa; Vázquez-Álvarez, Blancaa; Santos, José Luisc; Sánchez-Morla, Evac; Martínez, José Luisb; Aparicio, Anac; Peláez, José Carlosb; Cabranes Díaz, José Antoniob

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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.

© 2010 Lippincott Williams & Wilkins, Inc.


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