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