Polygenic Risk Score Assessment for Coronary Artery Disease in Asian Indians

Madhusmita Rout; Gurleen Kaur Tung; Jai Rup Singh; Narinder Kumar Mehra; Gurpreet S Wander; Sarju Ralhan; Dharambir K Sanghera

doi:10.1007/s12265-024-10511-z

Polygenic Risk Score Assessment for Coronary Artery Disease in Asian Indians

J Cardiovasc Transl Res. 2024 Apr 24. doi: 10.1007/s12265-024-10511-z. Online ahead of print.

Authors

Madhusmita Rout¹, Gurleen Kaur Tung¹, Jai Rup Singh², Narinder Kumar Mehra³, Gurpreet S Wander⁴, Sarju Ralhan⁴, Dharambir K Sanghera^{5

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Affiliations

¹ Department of Pediatrics, Section of Genetics, College of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., Rm 317 BMSB, Oklahoma City, OK, 73104, USA.
² Guru Nanak Dev University, Amritsar, Punjab, India.
³ All India Institute of Medical Sciences and Research, New Delhi, India.
⁴ Hero DMC Heart Institute, Ludhiana, Punjab, India.
⁵ Department of Pediatrics, Section of Genetics, College of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., Rm 317 BMSB, Oklahoma City, OK, 73104, USA. Dharambir-sanghera@ouhsc.edu.
⁶ Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Dharambir-sanghera@ouhsc.edu.
⁷ Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Dharambir-sanghera@ouhsc.edu.
⁸ Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Dharambir-sanghera@ouhsc.edu.
⁹ Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Dharambir-sanghera@ouhsc.edu.

PMID: 38658478
DOI: 10.1007/s12265-024-10511-z

Abstract

We evaluated the performance of various polygenic risk score (PRS) models derived from European (EU), South Asian (SA), and Punjabi Asian Indians (AI) studies on 13,974 subjects from AI ancestry. While all models successfully predicted Coronary artery disease (CAD) risk, the AI, SA, and EU + AI were superior predictors and more transportable than the EU model; the predictive performance in training and test sets was 18% and 22% higher in AI and EU + AI models, respectively than in EU. Comparing individuals with extreme PRS quartiles, the AI and EU + AI captured individuals with high CAD risk showed 2.6 to 4.6 times higher efficiency than the EU. Interestingly, including the clinical risk score did not significantly change the performance of any genetic model. The enrichment of diversity variants in EU PRS improves risk prediction and transportability. Establishing population-specific normative and risk factors and inclusion into genetic models would refine the risk stratification and improve the clinical utility of CAD PRS.

Keywords: Asian Indians; Clinical risk score; Coronary artery disease; Polygenic risk score.

Abstract

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