Headache Outpatient Centre, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
Headache. 2011 May;51(5):796-803. doi: 10.1111/j.1526-4610.2011.01858.x. Epub 2011 Mar 11.
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 rs10994336[T] in the ANK3 gene and rs1006737[A] in the CACNA1C gene and risk of bipolar disorder.
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.
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.
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.
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.
偏头痛和双相情感障碍的共病率很高，最近有人假设这两种疾病具有共同的家族遗传基础。全基因组关联研究强烈表明，ANK3 基因中的 rs10994336[T]多态性和 CACNA1C 基因中的 rs1006737[A]多态性与双相情感障碍的风险之间存在关联。
本研究旨在通过调查与儿童偏头痛患者相关的 2 种双相情感障碍风险多态性的家族传递，评估偏头痛与双相情感障碍之间存在遗传连锁的假设，该研究样本为具有儿童偏头痛的家系三体型患者和无关对照。
我们的样本包括 192 个家系三体型，每个三体型均有一个儿童偏头痛（137 例无先兆偏头痛，44 例有先兆偏头痛）的先证者和 228 个无关对照。使用 TaqMan 单核苷酸多态性基因分型测定法对 rs10994336 和 rs1006737 进行基因分型。使用 UNPHASED 程序对家系三体型进行等位基因和基因型传递不平衡检验分析，并对病例对照进行分析。
在偏头痛整体（rs10994336：OR=1.61，P=0.11；rs1006737：OR=1.12，P=0.49）和无先兆偏头痛和有先兆偏头痛亚组中，2 个标记物的等位基因和基因型传递不平衡检验分析均未显示出任何传递扭曲的证据。同样，等位基因和基因型频率的病例对照分析也未显示出任何关联的证据。
在本研究中，我们没有发现双相情感障碍风险多态性 rs10994336 在 ANK3 基因和 rs1006737 在 CACNA1C 基因与偏头痛之间存在关联的证据。然而，由于这些变体对双相情感障碍的风险影响较小（OR<1.5），因此，在本样本量下，我们不能排除它们对偏头痛易感性产生类似的小影响。
