No association between bipolar disorder risk polymorphisms in ANK3 and CACNA1C and common migraine

(Headache 2011;51:713‐725) Background.— Migraine and bipolar disorder are characterized by a high level of co‐morbidity, and a common familial–genetic basis has recently been hypothesized for the 2 disorders. Genome‐wide association studies have reported strong evidence of association between the polymorphisms rs10994336T] in the ANK3 gene and rs1006737A] in the CACNA1C gene and risk of bipolar disorder. Objective.— The aim of this study was to evaluate the hypothesis of a genetic linkage between migraine and bipolar disorder by investigating the familial transmission of the 2 bipolar disorder risk polymorphisms, in a sample of family trios with probands with childhood migraine, and unrelated controls. Methods.— Our sample comprised 192 family trios, each with a proband with childhood migraine (137 migraine without aura, 44 migraine with aura) and 228 unrelated controls. The markers rs10994336 and rs1006737 were genotyped using a TaqMan single nucleotide polymorphism Genotyping Assay. The transmission disequilibrium test analysis for the family trios and the case–control analysis were performed using the program UNPHASED. Results.— The allelic and genotypic transmission disequilibrium test analysis did not show any evidence of transmission distortion of the 2 markers in both migraine overall (rs10994336: OR = 1.61, P = .11; rs1006737: OR = 1.12, P = .49) and in the migraine without aura and migraine with aura subgroups. Likewise, the case–control analysis of alleles and genotypes frequencies did not show any evidence of association. Conclusion.— In the present study, we did not find evidence for association between the bipolar disorder risk polymorphisms rs10994336 in the ANK3 gene and rs1006737 in the CACNA1C gene in migraine. However, as these are variants that have a small effect on the risk of bipolar disorder (OR < 1.5), we cannot exclude a similar small effect on migraine susceptibility with the present sample size.