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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

doi: 10.1097/YPG.0b013e32833a9b7a
Original Articles

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.

aBiomedical Research Foundation

bDepartment of Psychiatry, Clínico San Carlos Hospital, Madrid

cDepartment of Psychiatry, Virgen de La Luz Hospital, Cuenca, Spain

Correspondence to Dr Jose Antonio Cabranes Díaz, MD, PhD, Instituto de Psiquiatría y Salud Mental, CIBERSAM, Clínico San Carlos Hospital, Martín Lagos s/n 28040, Madrid, Spain

Tel: +34 91 330 38 08; fax: +34 91 330 35 74;


Inés Ancín and Ana Barabash contributed equally to this study

Received 9 December 2009 Revised 1 March 2010 Accepted 1 April 2010

© 2010 Lippincott Williams & Wilkins, Inc.