Elucidation of genetic determinants of dyslipidaemia using a global screening array for the early detection of coronary artery disease.

IF 2.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Mammalian Genome Pub Date : 2023-12-01 Epub Date: 2023-09-05 DOI:10.1007/s00335-023-10017-0
Ananthaneni Radhika, Sandeepta Burgula, Chandan Badapanda, Tajamul Hussain, Shaik Mohammad Naushad
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Abstract

Dyslipidemia is a major risk factor for the development of coronary artery disease (CAD). Understanding the genetic determinants of dyslipidemia can provide valuable information on the pathogenesis of CAD and aid in the development of early detection strategies. In this study, we used a Global Screening Array (GSA) to elucidate the genetic factors associated with dyslipidemia and their potential role in the prediction of CAD. We conducted a GSA-based association study in 265 subjects to identify the genetic loci associated with dyslipidemia traits using Multiple Linear Regression (MLR) and Logistic Regression (LR), Classification and Regression Tree (CART), and Manhattan plots. We identified an association between dyslipidemia and variants identified in genes such as JCAD, GLIS3, CD38, FN1, CELSR2, MTNR1B, GIPR, DYM, APOB, APOE, ADCY5. The MLR models explained 62%, 71%, and 81% of the variability in HDL, LDL, and triglycerides, respectively. The Area Under the Curve (AUC) values in the LR models of HDL, LDL, and triglycerides were 1.00, 0.94, and 0.95, respectively. CART models identified novel gene-gene interactions influencing the risk for dyslipidemia. To conclude, we have identified the association of 12 SNVs with dyslipidemia and demonstrated their clinical utility in four different models such as MLR, LR, CART, and Manhattan plots. The identified genetic variants and associated pathways shed light on the underlying biology of dyslipidemia and offer potential avenues for precision medicine strategies in the management of CAD.

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利用冠状动脉疾病早期检测的全球筛选阵列阐明血脂异常的遗传决定因素。
血脂异常是冠状动脉疾病(CAD)发展的主要危险因素。了解血脂异常的遗传决定因素可以为CAD的发病机制提供有价值的信息,并有助于制定早期检测策略。在这项研究中,我们使用全球筛查阵列(GSA)来阐明与血脂异常相关的遗传因素及其在预测CAD中的潜在作用。我们在265名受试者中进行了一项基于GSA的关联研究,以使用多元线性回归(MLR)和逻辑回归(LR)、分类和回归树(CART)以及曼哈顿图来确定与血脂异常特征相关的遗传基因座。我们确定了血脂异常与在基因如JCAD、GLIS3、CD38、FN1、CELSR2、MTNR1B、GIPR、DYM、APOB、APOE、ADCY5中鉴定的变体之间的关联。MLR模型分别解释了高密度脂蛋白、低密度脂蛋白和甘油三酯变化的62%、71%和81%。HDL、LDL和甘油三酯的LR模型中的曲线下面积(AUC)值分别为1.00、0.94和0.95。CART模型确定了影响血脂异常风险的新基因-基因相互作用。总之,我们已经确定了12种SNV与血脂异常的相关性,并在四种不同的模型中证明了它们的临床实用性,如MLR、LR、CART和Manhattan图。已确定的遗传变异和相关途径揭示了血脂异常的潜在生物学,并为CAD管理中的精确医学策略提供了潜在途径。
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来源期刊
Mammalian Genome
Mammalian Genome 生物-生化与分子生物学
CiteScore
4.00
自引率
0.00%
发文量
33
审稿时长
6-12 weeks
期刊介绍: Mammalian Genome focuses on the experimental, theoretical and technical aspects of genetics, genomics, epigenetics and systems biology in mouse, human and other mammalian species, with an emphasis on the relationship between genotype and phenotype, elucidation of biological and disease pathways as well as experimental aspects of interventions, therapeutics, and precision medicine. The journal aims to publish high quality original papers that present novel findings in all areas of mammalian genetic research as well as review articles on areas of topical interest. The journal will also feature commentaries and editorials to inform readers of breakthrough discoveries as well as issues of research standards, policies and ethics.
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