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


CONCLUSIONS
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.
Ancín
Inés
I
aBiomedical Research Foundation bDepartment of Psychiatry, Clínico San Carlos Hospital, Madrid cDepartment of Psychiatry, Virgen de La Luz Hospital, Cuenca, Spain.
Barabash
Ana
A
Vázquez-Álvarez
Blanca
B
Santos
José Luis
JL
Sánchez-Morla
Eva
E
Martínez
José Luis
JL
Aparicio
Ana
A
Peláez
José Carlos
JC
Díaz
José Antonio Cabranes
JA
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor