Parent-of-origin effects in MS
Parent-of-origin effects in MS
复制标题
MS 中的亲本效应
作者：
B. Herrera;S. Ramagopalan;M. Lincoln;S. Orton;M. Chao;A. Sadovnick;G. Ebers
背景：多发性硬化症（MS）是一种复杂的神经系统疾病，病因和遗传模式未知，但女性发病率不断增加。对阿姨/叔叔-侄女/侄子 (AUNN) 对的研究有可能揭示复杂的性状遗传，因为这一群体可以根据性别、多发性硬化症状态和父母来源分为八种不同的配对类型。方法：使用由 807 个长辈 MS 家庭组成的队列，其中有 938 个受影响的 AUNN 对，这些对是从基于加拿大人口的纵向数据库中确定的，我们通过将受影响的对分为可能的母系和父系特征来源来检查 MS 传播的差异。结果：我们观察到，与未受影响的父亲相比，通过未受影响的母亲建立的父辈关系数量有所增加 (p = 0.008)。为了限制多对家庭引入的混杂因素，对母系家庭和父系家庭的总数进行了比较，发现母系家庭的数量明显较高（p = 0.038）。与阿姨/叔叔的性别比例相比，受影响的侄女/侄子的女性与男性的性别比例较高（0.00042）。结论：这一观察结果独立证实了之前关于多发性硬化症 (MS) 易感性中“母本父母”效应的发现。这些发现凸显了长辈对的特殊贡献。这些未充分利用的配对可以根据受影响的阿姨叔叔、未受影响的传播父母和受影响的后代的性别来比较传播情况。这种策略对于寻求亲本效应的疾病可能特别有利。这些研究结果还独立证实了女性多发性硬化症发病率的增加，表明家族病例与一般多发性硬化症人群一样受到相同环境因素的影响。
Background: Multiple sclerosis (MS) is a complex neurologic disease of unknown etiology and inheritance pattern, but with increasing incidence among females. The study of aunt/uncle–niece/nephew (AUNN) pairs has potential to shed light on the on complex trait inheritance as this group can be divided into eight different pair types by gender, MS status, and parent of origin. Methods: Using a cohort of 807 avuncular MS families with 938 affected AUNN pairs ascertained from a longitudinal, population-based Canadian database, we examined differential MS transmission by separating affected pairs into likely maternal and paternal trait origin. Results: We observed an increased number of avuncular pairs connected through unaffected mothers compared to unaffected fathers (p = 0.008). To restrict confounders introduced by families with multiple pairs the overall number of maternal and paternal families were compared, to reveal a significantly higher number of maternal families (p = 0.038). Female-to-male sex ratios were higher among affected nieces/nephews when compared to the sex ratio for aunts/uncles (0.00042). Conclusions: This observation independently confirms previous findings of a “maternal parent-of-origin” effect in multiple sclerosis (MS) susceptibility. These findings highlight the special contribution that can be derived from avuncular pairs. These underutilized pairings can compare transmission by the gender of affected aunt–uncle, the unaffected transmitting parent, and by that of the affected offspring. This strategy may be especially profitable in diseases where parent-of-origin effects are being sought. These findings also independently confirm the increasing rate of MS in females, demonstrating that familial cases are influenced by the same environmental factors as the general MS population.