Generalized, focal, and combined epilepsies in families: New evidence for distinct genetic factors.
Generalized, focal, and combined epilepsies in families: New evidence for distinct genetic factors.
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DOI：
10.1111/epi.16732
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发表时间：
2020-12
期刊：
影响因子：
5.6
通讯作者：
Epi4K Consortium
中科院分区：
文献类型：
--
作者：
Ellis CA;Ottman R;Epstein MP;Berkovic SF;Epi4K Consortium
为了确定共享和不同的遗传影响的作用，全面和局灶性癫痫的个人表现出两种类型的功能（合并癫痫），并在家庭表现出全面和局灶性癫痫在单独的个人（混合家庭）。我们分析了多重家族（每个家族≥3个受影响个体）的表型确定的Epi4K队列，使用的方法量化了家族内表型的聚集和家族谱系内不同表型个体的相关性。该队列包括281个家庭，其中包含1，021名全身性癫痫患者（n = 484），局灶性癫痫患者（304），合并癫痫患者（51）或未分类癫痫患者（182）。合并癫痫患者的亲属中合并癫痫的几率高于其他癫痫类型患者的亲属（OR 5.2，95%CI 1.7，16.1，p = 0.004）。合并癫痫的个体在家庭中共同发生的几率比预期的要高（p = 0.03）。在混合家系中，每种类型的癫痫患者与同一类型的亲属的关系比与其他类型的亲属的关系更密切（p < 0.001）。这些研究结果表明，不同的遗传影响的基础上最近认识到的实体合并癫痫，就像全身性癫痫和局灶性癫痫各有不同的遗传影响。混合家庭可能部分反映了这些不同的遗传影响的机会共存。这些结论对癫痫的分子遗传学研究具有重要意义。
To determine the roles of shared and distinct genetic influences on generalized and focal epilepsy operating in individuals who manifest features of both types (combined epilepsies) and in families manifesting both generalized and focal epilepsies in separate individuals (mixed families). We analyzed the deeply-phenotyped Epi4K cohort of multiplex families (≥3 affected individuals per family) using methods that quantify the aggregation of phenotypes within families and the relatedness of individuals with different phenotypes within family pedigrees. The cohort included 281 families containing 1,021 individuals with generalized (n = 484), focal (304), combined (51), or unclassified (182) epilepsies. The odds of combined epilepsy was higher in relatives of participants with combined epilepsy than in relatives of those with other epilepsy types (OR 5.2, 95%CI 1.7, 16.1, p = 0.004). Individuals with combined epilepsy co-occurred in families more often than expected by chance (p = 0.03). Within mixed families, individuals with each type of epilepsy were more closely related to relatives with the same type than to relatives with other types (p < 0.001). These findings suggest that distinct genetic influences underlie the recently-recognized entity of combined epilepsies, just as generalized epilepsies and focal epilepsies each have distinct genetic influences. Mixed families may in part reflect chance co-occurrence of these distinct genetic influences. These conclusions have important implications for molecular genetic studies aimed at identifying genetic determinants of the epilepsies.
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