No evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene locus and bipolar disorder in the portuguese population

Recently we reported evidence for linkage disequilibrium and parent-of-origin effect between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. The CHRNA7 is involved in the P50 sensory gating deficits. Freedman et al. had found a positive correlation between the P50 gating deficit in schizophrenia and mania patients. We therefore proceeded to test whether the CHRNA7 genetic linkage extends beyond schizophrenia to include bipolar disorder. We genotyped markers D15S1360, D15S165 and L76630 in 19 bipolar disorder affected Portuguese families with 60 affected individuals and 62 unaffected family members. Linkage analysis by GENEHUNTER did not reveal any significant associations for CHRNA7 in bipolar disorder. D15S1360 results: LOD=-4.93, NPL = 0.15, P = 0.42. D15S165 results: LOD=-15.28, NPL =-0.59, P = 0.76. L76630 results: LOD= -5.11, NPL =-0.091, P = 0.519. Results of ETDT analysis didn't reveal any significant linkage disequilibrium. Marker D15S1360 shows: allele-wise P = 0.14, genotype-wise P = 0.064. Marker D15S165 shows: allele-wise P = 0.62, genotype-wise P = 0.17. Marker L76630 shows: both the allele-wise and the genotype-wise P = 0.41. Analysis of 'maternal' and 'paternal' meioses has yielded no parent-of-origin effect for three polymorphisms in the entire sample of bipolar disorders. The results suggested no evidence of linkage disequilibrium and parent-of-ongin effect between CHRNA7 locus and bipolar disorder in the Portuguese families studied.