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Gene–gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy

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Abstract

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene–gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene–gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene–gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.

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Funding

The Fujian Provincial Health Technology Project (grant number 2019-ZQN-94) and the Natural Science Foundation of Fujian Province (grant number 2020J011257) funded the study. The funders had no role in study design, data collection, data analysis, data interpretation, and the decision to prepare or publish the manuscript.

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  1. Zhi-Jian Lin, Jun-Wei He, and Sheng-Yin Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, School of Clinical Medicine, the Affiliated Hospital of Putian UniversityFujian Medical UniversityBrain Science Institute of Putian University, 999 Dongzhen East Road, Licheng District, Putian, 351100, China

    Zhi-Jian Lin, Jun-Wei He, Sheng-Yin Zhu, Li-Hong Xue, Jian-Feng Zheng, Li-Qin Zheng, Bi-Xia Huang, Guo-Zhang Chen & Peng-Xing Lin

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  1. Zhi-Jian Lin
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Zhi-Jian Lin contributed to the conception and design of the study. Zhi-Jian Lin, Jun-Wei He, and Sheng-Yin Zhu performed material preparation, data collection, and data analysis. Zhi-Jian Lin wrote the first draft of the manuscript, and all authors commented on previous versions. All authors read and approved the final manuscript.

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Correspondence to Peng-Xing Lin.

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Lin, ZJ., He, JW., Zhu, SY. et al. Gene–gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy. Neurogenetics (2024). https://doi.org/10.1007/s10048-024-00748-w

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