Nyholt D R, Dawkins J L, Brimage P J, Goadsby P J, Nicholson G A, Griffiths L R
Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland 4217, Australia.
Hum Mol Genet. 1998 Mar;7(3):459-63. doi: 10.1093/hmg/7.3.459.
Migraine is a common complex disorder that shows strong familial aggregation. There is a general increased prevalence of migraine in females compared with males, with recent studies indicating that migraine affects 18% of females compared with 6% of males. This preponderance of females among migraine sufferers coupled with evidence of an increased risk of migraine in first degree relatives of male probands but not in relatives of female probands suggests the possibility of an X-linked dominant gene. We report here the localization of a typical migraine susceptibility locus to the X chromosome. Of three large multigenerational migraine pedigrees two families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigrees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the localization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male probands and may be involved in the increased female prevalence of this disorder.
偏头痛是一种常见的复杂疾病，具有很强的家族聚集性。与男性相比，女性偏头痛的总体患病率普遍更高，最近的研究表明，18%的女性患有偏头痛，而男性的这一比例为6%。偏头痛患者中女性占多数，同时有证据表明男性先证者的一级亲属患偏头痛的风险增加，而女性先证者的亲属则不然，这表明可能存在X连锁显性基因。我们在此报告一个典型的偏头痛易感基因座定位于X染色体。在三个大型多代偏头痛家系中，有两个家系显示与Xq标记存在显著的等位基因共享过剩（P = 0.031和P = 0.012）。对所有三个家系的数据进行总体分析，得到了支持连锁和异质性的显著证据（HLOD = 3.1）。这些发现提供了确凿的证据，表明家族性典型偏头痛是一种异质性疾病。我们认为，偏头痛易感基因座定位于X染色体可能部分解释了男性先证者亲属患偏头痛风险增加的原因，并且可能与该疾病女性患病率增加有关。
