Association Screen of High Priority Positional Candidate Genes for Migraine

典型的偏头痛是一种常见的、使人虚弱和痛苦的疾病，通常影响人们在最富有生产力的年龄（25%的女性和7.5%的男性）。世界卫生组织（World Health Organization）最近将偏头痛列为世界20大致残原因之一，其影响远远超出了患者个人，影响到了家庭和社区。尽管偏头痛在我们的社会中非常普遍，但其病因仍然相对模糊，也没有基于实验室的诊断测试来识别患有这种疾病的人。双胞胎研究表明，偏头痛具有显著的遗传成分，遗传率估计为33-65%。因此，为了确定这种疾病的分子机制，我们一直在寻找与偏头痛共遗传（相关）的基因组区域。由此产生的全基因组连锁扫描涉及756个澳大利亚家庭，发现了染色体5q21上存在一种新的偏头痛基因的重要证据，染色体10q22上存在一种基因的高度暗含证据。重要的是，我们最近在澳大利亚偏头痛家族的独立收集中复制了与5q21和10q22区域的联系。因此，在我们的样本中，这些区域对确定偏头痛易感基因有很大的希望。利用生物信息学计算机辅助检索公共数据库，我们对5q21和10q22区域内的潜在候选基因进行了排序。该项目将筛选768例病例和768例对照中的前21个候选基因，分别筛选家族性偏头痛的存在和不存在。我们提出的两个强烈相关区域的高优先级基因的关联筛选对确定常见偏头痛易感性的基因具有很高的功效。这些基因将为进一步阐明偏头痛的复杂分子途径提供线索，并最终有助于诊断测试和合理治疗策略的发展。

Typical migraine, is a frequent, debilitating and painful disorder that normally affects people during their most productive years (25% of females and 7.5% of males). The World Health Organization recently identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond the suffering individual, to the family and community. Although migraine is highly prevalent in our society, its aetiology remains relatively obscure and there are no laboratory based diagnostic tests that identify those who suffer from the disorder. Twin studies indicate that migraine has a significant genetic component, with heritability estimates of 33-65%. Therefore, in an effort to identify the molecular mechanisms underlying the disorder, we have been looking for genomic regions co-inherited (linked) with migraine. The resulting genome-wide linkage scan involving 756 Australian families found significant evidence for the presence of a novel migraine gene on chromosome 5q21 and highly suggestive evidence for a gene on chromosome 10q22. Importantly, we recently replicated linkage to the 5q21 and 10q22 regions in an independent collection of Australian migraine families. Consequently, these regions hold great promise for identifying migraine susceptibility genes in our sample. Using a bioinformatics computer-assisted search of public databases we have ranked the potential candidature of the genes within the 5q21 and 10q22 regions This project will screen the top 21 candidate genes in 768 cases and 768 controls highly selected for the presence and absence of familial migraine, respectively. Our proposed association screen of high priority genes in two strongly implicated regions has high power to identify genes underlying common migraine susceptibility. Such genes will provide clues to the further elucidation of the complex molecular pathways of migraine and , finally, will help in the development of diagnostic tests and rational treatment strategies.