Whole-genome linkage scan for epilepsy-related photosensitivity: A mega-analysis
Whole-genome linkage scan for epilepsy-related photosensitivity: A mega-analysis
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DOI：
10.1016/j.eplepsyres.2010.01.013
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发表时间：
2010-05-01
影响因子：
2.2
通讯作者：
Koeleman, B. P. C.
中科院分区：
文献类型：
--
作者：
de Kovel, C. G. F.;Pinto, D.;Koeleman, B. P. C.
光性发作反应（PPR）被认为是特发性全身性癫痫（IGE）的一个危险因素，它有很强的遗传基础。此前发表的两项全基因组连锁研究发现，PPR的位点位于6p21、7q32、13q13、13q31和16p13。在这里，我们将这些研究结合起来，加上额外的家庭，对100个家庭进行了大型分析。非参数连锁分析确定了三个提示的光敏性峰，其中两个是新发现的（5q35.3和8q21.13），一个是以前发现的（16p13.3）。我们没有发现先前检测到的四个位点（6p21、7q32、13q13和13q31）存在连锁的证据。我们的研究结果表明，不同的家庭数据集与一个共同的基因座没有联系。详细分析表明，16p13位点的峰主要受到单个家族子集的支持，而5q35和8q21位点的峰受到多个家族子集的微弱支持。家庭研究明确支持小反刍反应作为IGE的危险因素的作用。这项大型分析表明，不同的基因座似乎与ppr阳性家族的亚群有关，这些亚群可能在微妙的临床表型或地理起源上有所不同。因此，小反刍兽疫的进一步连锁研究应包括深入的表型分析，以建立适当的亚群并增加遗传同质性。(C) 2010 Elsevier B.V.版权所有
Photoparoxysmal response (PPR) is considered to be a risk factor for idiopathic generalised epilepsy (IGE) and it has a strong genetic basis. Two genome-wide linkage studies have been published before and they identified loci for PPR at 6p21, 7q32, 13q13, 13q31 and 16p13. Here we combine these studies, augmented with additional families, in a mega-analysis of 100 families. Non-parametric linkage analysis identified three suggestive peaks for photosensitivity, two of which are novel (5q35.3 and 8q21.13) and one has been found before (16p13.3). We found no evidence for linkage at four previously detected loci (6p21, 7q32, 13q13 and 13q31).Our results suggest that the different family data sets are not linked to a shared locus. Detailed analysis showed that the peak at 16p13 was mainly supported by a single subset of families, while the peaks at 5q35 and 8q21 had weak support from multiple subsets.Family studies clearly support the role of PPR as a risk factor for IGE. This mega-analysis shows that distinct loci seem to be linked to subsets of PPR-positive families that may differ in subtle clinical phenotypes or geographic origin. Further linkage studies of PPR should therefore include in-depth phenotyping to make appropriate subsets and increase genetic homogeneity. (C) 2010 Elsevier B.V. All rights reserved.