Predicting late-stage age-related macular degeneration by integrating marginally weak SNPs in GWA studies.
Predicting late-stage age-related macular degeneration by integrating marginally weak SNPs in GWA studies.
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DOI：
10.3389/fgene.2023.1075824
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发表时间：
2023
影响因子：
3.7
通讯作者：
Chen, Wei
中科院分区：
文献类型：
--
作者：
Zhou, Xueping;Zhang, Jipeng;Ding, Ying;Huang, Heng;Li, Yanming;Chen, Wei
关键词：
年龄相关性黄斑变性（AMD）是一种进行性神经退行性疾病，是发达国家致盲的主要原因。目前针对晚期年龄相关性黄斑变性的全基因组关联研究（GWAS）主要是基于单标记的方法，每次研究一个单核苷酸多态性（SNP），并推迟了下游精细映射中标记间连锁不平衡（LD）信息的整合。最近的研究表明，将标记间连接/相关性直接纳入变异检测有助于发现传统全基因组关联研究中经常遗漏的新的微弱单核苷酸多态性，也有助于提高疾病预测的准确性。方法：首先进行单标记分析，检测边缘强单核苷酸多态性。然后利用全基因组连锁不平衡谱对检测到的每一个强单核苷酸多态性寻找高连锁不平衡连接的单核苷酸多态性簇。通过与检测到的单核苷酸多态性簇的联合线性判别模型选择边际弱单核苷酸多态性。根据选择的强、弱单核苷酸多态性进行预测。结果：先前确定的几个与晚期年龄相关的黄斑变性易感基因，如BTBD16、C3、CFH、CFHR3、HTARA1得到证实。新基因DENND1B、PLK5、ARHGAP45和BAG6被发现为微弱信号。总体预测精度分别为76.8%和73.2%。结论：从整合标记间连锁不平衡信息中检测到的微弱单核苷酸多态性可能对年龄相关性黄斑变性具有很强的预测作用。检测和整合这些微弱的信号有助于更好地了解与年龄相关的黄斑变性的潜在疾病发展机制和更准确的预后。
Introduction: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease and the leading cause of blindness in developed countries. Current genome-wide association studies (GWAS) for late-stage age-related macular degeneration are mainly single-marker-based approaches, which investigate one Single-Nucleotide Polymorphism (SNP) at a time and postpone the integration of inter-marker Linkage-disequilibrium (LD) information in the downstream fine mappings. Recent studies showed that directly incorporating inter-marker connection/correlation into variants detection can help discover novel marginally weak single-nucleotide polymorphisms, which are often missed in conventional genome-wide association studies, and can also help improve disease prediction accuracy. Methods: Single-marker analysis is performed first to detect marginally strong single-nucleotide polymorphisms. Then the whole-genome linkage-disequilibrium spectrum is explored and used to search for high-linkage-disequilibrium connected single-nucleotide polymorphism clusters for each strong single-nucleotide polymorphism detected. Marginally weak single-nucleotide polymorphisms are selected via a joint linear discriminant model with the detected single-nucleotide polymorphism clusters. Prediction is made based on the selected strong and weak single-nucleotide polymorphisms. Results: Several previously identified late-stage age-related macular degeneration susceptibility genes, for example, BTBD16, C3, CFH, CFHR3, HTARA1, are confirmed. Novel genes DENND1B, PLK5, ARHGAP45, and BAG6 are discovered as marginally weak signals. Overall prediction accuracy of 76.8% and 73.2% was achieved with and without the inclusion of the identified marginally weak signals, respectively. Conclusion: Marginally weak single-nucleotide polymorphisms, detected from integrating inter-marker linkage-disequilibrium information, may have strong predictive effects on age-related macular degeneration. Detecting and integrating such marginally weak signals can help with a better understanding of the underlying disease-development mechanisms for age-related macular degeneration and more accurate prognostics.
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影响因子：
1.8
作者：
Gibbs, Daniel;Yang, Zhenglin;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
3.7
作者：
Goudey B;Abraham G;Kikianty E;Wang Q;Rawlinson D;Shi F;Haviv I;Stern L;Kowalczyk A;Inouye M
通讯作者：
Inouye M
影响因子：
14.9
作者：
Andrysik Z;Bernstein WZ;Deng L;Myer DL;Li YQ;Tischfield JA;Stambrook PJ;Bahassi el M
通讯作者：
Bahassi el M
DOI：
10.1097/opx.0000000000000322
发表时间：
2014-08
期刊：
Optometry and vision science : official publication of the American Academy of Optometry
影响因子：
--
作者：
Fletcher EL;Jobling AI;Greferath U;Mills SA;Waugh M;Ho T;de Iongh RU;Phipps JA;Vessey KA
通讯作者：
Vessey KA
影响因子：
4
作者：
Amado-Azevedo, J.;Reinhard, N. R.;Hordijk, P. L.
通讯作者：
Hordijk, P. L.