AUTHOR=Song Meng , Liu Jiewei , Yang Yongfeng , Lv Luxian , Li Wenqiang , Luo Xiong-Jian 

TITLE=Genome-Wide Meta-Analysis Identifies Two Novel Risk Loci for Epilepsy

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.722592

DOI=10.3389/fnins.2021.722592

ISSN=1662-453X

ABSTRACT=<p>Epilepsy (affects about 70 million people worldwide) is one of the most prevalent brain disorders and imposes a huge economic burden on society. Epilepsy has a strong genetic component. In this study, we perform the largest genome-wide meta-analysis of epilepsy (<italic>N</italic> = 8,00,869 subjects) by integrating four large-scale genome-wide association studies (GWASs) of epilepsy. We identified three genome-wide significant (GWS) (<italic>p</italic> &lt; 5 × 10<sup>–8</sup>) risk loci for epilepsy. The risk loci on 7q21.11 [lead single nucleotide polymorphism (SNP) rs11978015, <italic>p</italic> = 9.26 × 10<sup>–9</sup>] and 8p23.1 (lead SNP rs28634186, <italic>p</italic> = 4.39 × 10<sup>–8</sup>) are newly identified in the present study. Of note, rs11978015 resides in upstream of <italic>GRM3</italic>, which encodes glutamate metabotropic receptor 3. <italic>GRM3</italic> has pivotal roles in neurotransmission and is involved in most aspects of normal brain function. In addition, we also identified three genes (<italic>TTC21B</italic>, <italic>RP11-375N15.2</italic>, and <italic>TNKS</italic>) whose <italic>cis-</italic>regulated expression level are associated with epilepsy, indicating that risk variants may confer epilepsy risk through regulating the expression of these genes. Our study not only provides new insights into genetic architecture of epilepsy but also prioritizes potential molecular targets (including <italic>GRM3</italic> and <italic>TTC21B</italic>) for development of new drugs and therapeutics for epilepsy.</p>