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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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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This study was funded by intramural grants provided by the management of Yoda LifeLine diagnostics Pvt Ltd, Hyderabad.
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SMN, SB and TH conceived and designed this study. AR, BC, and SMN performed the biochemical and genetic analyses. SMN, AR and BC wrote the main manuscript text. SB and TH reviewed the content. All the authors finalized the manuscript.
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Radhika, A., Burgula, S., Badapanda, C. et al. Elucidation of genetic determinants of dyslipidaemia using a global screening array for the early detection of coronary artery disease. Mamm Genome 34, 632–643 (2023). https://doi.org/10.1007/s00335-023-10017-0
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DOI: https://doi.org/10.1007/s00335-023-10017-0