IF 2.9 3区 医学 Q2 GENETICS & HEREDITY
Sarita Thakran, Debleena Guin, Priyanka Singh, Bharathram Uppili, Srinivasan Ramachandran, Suman S Kushwaha, Ritushree Kukreti
{"title":"Genome-Wide Association Study Reveals Genetic Architecture of Common Epilepsies.","authors":"Sarita Thakran, Debleena Guin, Priyanka Singh, Bharathram Uppili, Srinivasan Ramachandran, Suman S Kushwaha, Ritushree Kukreti","doi":"10.1111/cge.14710","DOIUrl":null,"url":null,"abstract":"<p><p>Epilepsy, affecting approximately 50 million individuals worldwide, exhibits a genetic heritability of 32%. While several genes/loci associated with epilepsy have been identified through candidate and genome-wide association studies (GWAS), exploration of population-specific markers remains underexplored. We conducted the first GWAS in north Indian population (~1500 samples) to identify genetic variants/loci associated with epilepsy risk, validated using targeted next-generation sequencing (NGS). Our GWAS revealed 30 variants across seven loci associated with epilepsy risk, including six novel loci. Subtype analysis based on etiology and seizure types, identified 57 variants across 11 loci, 10 of which are novel. Gene-set analysis unveiled enrichment in genes associated with glutathione synthesis and recycling and regulation of dopaminergic neuron differentiation pivotal in epilepsy pathophysiology. Furthermore, PRS analysis revealed a significant genetic contribution to the epilepsy with an R<sup>2</sup> of 0.00573. Additionally, targeted NGS showed ~95% concordance with GSA genotypes. Our study highlights six novel loci rs17031055/4q31.3(DCHS2), rs73182224/3q27.2(DGKG), rs9322462/6q25.2(CNKSR3), rs75328617/8q24.23(RNU1-35P), rs2938010/10q26.13(CTBP2) and rs11652575/17p11.2(SLC5A10) associated with epilepsy risk. These findings offer valuable insights into the genetic landscape of epilepsy in the north Indian population, providing foundation for future exploratory studies.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.14710","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

全世界约有 5000 万人患有癫痫,其遗传率高达 32%。虽然通过候选基因和全基因组关联研究(GWAS)已确定了几个与癫痫相关的基因/基因组,但对人群特异性标记的探索仍然不足。我们首次在北印度人群(约 1,500 个样本)中进行了 GWAS,以确定与癫痫风险相关的基因变异/基因组,并使用靶向下一代测序(NGS)进行了验证。我们的 GWAS 发现了与癫痫风险相关的 7 个位点上的 30 个变体,其中包括 6 个新的位点。基于病因学和癫痫发作类型的亚型分析发现了 11 个基因位点上的 57 个变异,其中 10 个是新变异。基因集分析揭示了与谷胱甘肽合成和循环以及癫痫病理生理学中关键的多巴胺能神经元分化调控相关的基因的富集。此外,PRS 分析表明,R2 值为 0.00573 的基因对癫痫有显著影响。此外,靶向 NGS 与 GSA 基因型的一致性达到约 95%。我们的研究强调了与癫痫风险相关的六个新位点 rs17031055/4q31.3(DCHS2)、rs73182224/3q27.2(DGKG)、rs9322462/6q25.2(CNKSR3)、rs75328617/8q24.23(RNU1-35P)、rs2938010/10q26.13(CTBP2)和 rs11652575/17p11.2(SLC5A10)。这些发现为了解北印度人群的癫痫遗传情况提供了宝贵的信息,为今后的探索性研究奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genome-Wide Association Study Reveals Genetic Architecture of Common Epilepsies.

Epilepsy, affecting approximately 50 million individuals worldwide, exhibits a genetic heritability of 32%. While several genes/loci associated with epilepsy have been identified through candidate and genome-wide association studies (GWAS), exploration of population-specific markers remains underexplored. We conducted the first GWAS in north Indian population (~1500 samples) to identify genetic variants/loci associated with epilepsy risk, validated using targeted next-generation sequencing (NGS). Our GWAS revealed 30 variants across seven loci associated with epilepsy risk, including six novel loci. Subtype analysis based on etiology and seizure types, identified 57 variants across 11 loci, 10 of which are novel. Gene-set analysis unveiled enrichment in genes associated with glutathione synthesis and recycling and regulation of dopaminergic neuron differentiation pivotal in epilepsy pathophysiology. Furthermore, PRS analysis revealed a significant genetic contribution to the epilepsy with an R2 of 0.00573. Additionally, targeted NGS showed ~95% concordance with GSA genotypes. Our study highlights six novel loci rs17031055/4q31.3(DCHS2), rs73182224/3q27.2(DGKG), rs9322462/6q25.2(CNKSR3), rs75328617/8q24.23(RNU1-35P), rs2938010/10q26.13(CTBP2) and rs11652575/17p11.2(SLC5A10) associated with epilepsy risk. These findings offer valuable insights into the genetic landscape of epilepsy in the north Indian population, providing foundation for future exploratory studies.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信