Genetic dissection of the common epilepsies

被引:21
作者
Tan, NCK
Mulley, JC
Scheffer, IE
机构
[1] Univ Melbourne, Austin Hlth, Epilepsy Res Ctr, Heidelberg West, Vic 3081, Australia
[2] Natl Inst Neurosci, Dept Neurol, Singapore, Singapore
[3] Childrens Hosp, Dept Med Genet, Adelaide, SA, Australia
[4] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia
[5] Royal Childrens Hosp, Dept Paediat, Parkville, Vic 3052, Australia
[6] Univ Melbourne, Austin Hlth, Dept Med Neurol, Heidelberg West, Vic 3081, Australia
关键词
complex disease; endophenotyping; genetic dissection; genetic heterogeneity;
D O I
10.1097/01.wco.0000218232.66054.46
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Purpose of review Only two functionally validated susceptibility genes, CACNA1H and GABRD, have so far been identified in the, common epilepsies using a candidate gene approach. The difficulty with the alternative statistical approach, where none of the suggested candidates has been functionally validated, may partly be due to the posited genetic architecture of the common epilepsies, such as the idiopathic generalized epilepsies. A subset of both rare and common variants from a much larger pool of susceptibility genes may contribute to disease risk. We review methods and designs for the genetic dissection of common epilepsies. Recent findings Genetic association studies, though theoretically more powerful than linkage analysis, have not yet delivered validated susceptibility genes. Methodological flaws can undermine such studies but are correctable. Concerns remain, however, about the extent of underlying genetic heterogeneity in common epilepsies. Genome-wide association studies are increasingly feasible, but issues remain about their conduct and analysis. Metaanalysis may resolve conflicting association studies, facilitated by the establishment of databases of genetic association studies. Newer multi-locus and admixture mapping approaches are attractive alternatives to traditional association studies and may offer new insights into identifying epilepsy genes. Summary We conclude by emphasizing the importance of deeper endophenotyping using electroclinical, imaging, and molecular approaches to dissect the common epilepsies.
引用
收藏
页码:157 / 163
页数:7
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