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Polygenic Risk Score Assessment for Coronary Artery Disease in Asian Indians

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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.

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Data Availability

A part of the AIDHS/SDS data used in this study has already been deposited on the DbGap repository of the National Institutes of Health (https://www.ncbi.nlm.nih.gov/gap/). The additional datasets used and/or analyzed during the current study would be available from the corresponding author on reasonable request.

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Acknowledgements

The Asian Indian Diabetic Heart Study/Sikh Diabetes Study was supported by National Institute of Health grants-R01DK082766 and R01DK118427 (National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK) and the Presbyterian Health Foundation grants. The authors thank all the participants of AIDHS/SDS and are grateful for their contribution to this study. Technical support and genotype data generation by Adam Adler from the Oklahoma Medical Research Foundation are duly acknowledged.

Funding

The Asian Indian Diabetic Heart Study/Sikh Diabetes Study was supported by National Institute of Health grants-R01DK082766 and R01DK118427 (National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK) and the Presbyterian Health Foundation grants.

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Authors and 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

    Madhusmita Rout, Gurleen Kaur Tung & Dharambir K. Sanghera

  2. Guru Nanak Dev University, Amritsar, Punjab, India

    Jai Rup Singh

  3. All India Institute of Medical Sciences and Research, New Delhi, India

    Narinder Kumar Mehra

  4. Hero DMC Heart Institute, Ludhiana, Punjab, India

    Gurpreet S. Wander & Sarju Ralhan

  5. Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Dharambir K. Sanghera

  6. Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Dharambir K. Sanghera

  7. Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Dharambir K. Sanghera

  8. Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Dharambir K. Sanghera

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  1. Madhusmita Rout
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Contributions

MR and GKT performed data analysis and helped in manuscript preparation; JRS, NKM, GSW, and SR contributed to recruitment and phenoty** for AIDHS/SDS. DKS designed the study, contributed to genoty** and phenoty** as a cohort PI of AIDHS/SDS, and wrote the manuscript.

Corresponding author

Correspondence to Dharambir K. Sanghera.

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Ethics Approval and Consent to Participate

The study was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (IRB#2911), as well as the Human Subject Protection Committee at the participating hospitals and institutes in India and informed consent was obtained from all the participants included in the study. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5).

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The authors declare that they have no competing interests.

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Rout, M., Tung, G.K., Singh, J.R. et al. Polygenic Risk Score Assessment for Coronary Artery Disease in Asian Indians. J. of Cardiovasc. Trans. Res. (2024). https://doi.org/10.1007/s12265-024-10511-z

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