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

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

doi:10.3389/fnins.2021.722592

Cited by 14 publications

(14 citation statements)

References 52 publications

(82 reference statements)

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“…Other genetic and environmental modifiers are likely to account for much of the remaining phenotypic variability, but these factors remain difficult to be fully established and characterized. This has been shown in different research works with functional studies, with relevant translational implications in genetic-phenotypic correlations, such as the case of some biallelic variants in SCN1B [20] .…”

Section: Phenotypic Expansionmentioning

confidence: 83%

Developmental and epileptic encephalopathies after negative or inconclusive genetic testing: what is next?

Aledo‐Serrano¹,

Sánchez-Alcudia²,

Toledano³

et al. 2021

jtgg

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The redefinition of classical electroclinical syndromes and the emergence of neurogenetics has led to a revolution in the field of developmental and epileptic encephalopathies (DEEs). In this context, advances in genetic techniques are leading to the final diagnosis of a large proportion of patients with DEE. However, up to 50% of patients with DEE remain undiagnosed. For patients with uncertain genetic etiology, there is a pressing need for the implementation of new targeted treatments and precision medicine. In some undiagnosed patients, genetic reanalysis with further in-depth or reverse phenotyping are valuable diagnostic tools to clarify new variants of uncertain significance. In other cases, the implementation of new bioinformatic algorithms is required for the update and reassessment of previously generated genetic data. Moreover, many other clinical tools have been developed for the management of patients of DEEs after a negative or inconclusive genetic testing. In this review, we highlight advances and limitations of new diagnostic strategies used in DEE patients without a known genetic etiology. Finally, we provide a wide perspective on aspects that will need further research, especially in non-Mendelian inheritance DEEs, such as those related to somatic mosaicism of the central nervous system or epigenetic and oligogenic mechanisms.

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Section: Phenotypic Expansionmentioning

confidence: 83%

Developmental and epileptic encephalopathies after negative or inconclusive genetic testing: what is next?

Aledo‐Serrano¹,

Sánchez-Alcudia²,

Toledano³

et al. 2021

jtgg

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“…Genome‐wide association studies (GWASs) have previously been conducted for other common epilepsies, and have informed their diverse biological mechanisms [36–38]. However, no GWAS has been conducted to test the genetic association with PTE or PSE.…”

Section: Discussionmentioning

confidence: 99%

Impact of genetic polymorphisms on the risk of epilepsy amongst patients with acute brain injury: A systematic review

Misra

Quinn

Falcone

et al. 2023

Euro J of Neurology

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Background and purpose:The genetics of late seizure or epilepsy secondary to traumatic brain injury (TBI) or stroke are poorly understood. We undertook a systematic review to test the association of single-nucleotide polymorphisms (SNPs) with the risk of posttraumatic epilepsy (PTE) and post-stroke epilepsy (PSE). Methods:We followed methods from our prespecified protocol on PROSPERO to identify indexed articles for this systematic review. We collated the association statistics from the included articles to assess the association of SNPs with the risk of epilepsy amongst TBI or stroke patients. We assessed study quality using the Q-Genie tool. We report odds ratios (OR) and hazard ratios with 95% confidence intervals (CIs). Results:The literature search yielded 420 articles. We included 16 studies in our systematic review, of which seven were of poor quality. We examined published data on 127 SNPs from 32 genes identified in PTE and PSE patients. Eleven SNPs were associated with a significantly increased risk of PTE. Three SNPs, TRMP6 rs2274924, ALDH2 rs671, and CD40 -1C/T, were significantly associated with an increased risk of PSE, while two, AT1R rs12721273 and rs55707609, were significantly associated with reduced risk. The meta-analysis for the association of the APOE ɛ4 with PTE was nonsignificant (OR 1.8, CI 0.6-5.6). Conclusions:The current evidence on the association of genetic polymorphisms in epilepsy secondary to TBI or stroke is of low quality and lacks validation. A collaborative effort to pool genetic data linked to epileptogenesis in stroke and TBI patients is warranted.

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“…Це можна пояснити різною наявністю найбільш поширених зовнішніх чинників ризику та приховуванням цього стану у жінок з соціокультурних причин. (Fiest et al, 2017;Song et al, 2021).…”

Section: генетика епілепсіїunclassified

The Genetics of Epilepsy

Pomohaibo¹,

Berezan²,

Petrushov³

2022

ПІO

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Epilepsy is a group of painful conditions caused by brain disorders, which are characterized by a persistent predisposition to epileptic seizures, as well as neurobiological, cognitive, psychological and social consequences. Currently, the overall prevalence of epilepsy in the world's population is 0.88% and ranges from 0.64% in developed countries to 1.00% in other countries. The prevalence of epilepsy in men is slightly higher than in women, and heredity varies between 25%-70%. According to the current classification, epilepsy includes four main forms: focal epilepsy, generalized epilepsy, combined focal and generalized epilepsy, and indeterminate epilepsy. The most common form of epilepsy is focal epilepsy, which accounts for 60% of all epilepsies. Currently, 14 genes associated with the development of epilepsy have been described, the functions of which are impaired by the presence of single nucleotide polymorphisms (SNPs). These SNPs can be located not only in the coding regions of genes (exons) or regulatory regions (eg., promoters), but also in their non-coding regions (introns), as well as in intergenic regions of DNA near a particular gene. Further research into the genetics of epilepsy should focus on developing new analytical approaches that will help uncover the unknown molecular genetic mechanisms of this group of disorders. Advances in the genetics of epilepsy will have a positive impact on clinical practice.

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

Cited by 14 publications

References 52 publications

Developmental and epileptic encephalopathies after negative or inconclusive genetic testing: what is next?

Developmental and epileptic encephalopathies after negative or inconclusive genetic testing: what is next?

Impact of genetic polymorphisms on the risk of epilepsy amongst patients with acute brain injury: A systematic review

The Genetics of Epilepsy

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