Assessing the performance of European-derived cardiometabolic polygenic risk scores in South-Asians and their interplay with family history

HASSANIN, Emadeldin Saeed Fathy Sayed; MAY, Patrick; BOBBILI, Dheeraj Reddy

doi:10.1186/s12920-023-01598-5

Article (Scientific journals)

Assessing the performance of European-derived cardiometabolic polygenic risk scores in South-Asians and their interplay with family history

HASSANIN, Emadeldin Saeed Fathy Sayed; MAY, Patrick; BOBBILI, Dheeraj Reddy

2023 • In BMC Medical Genomics

Peer Reviewed verified by ORBi

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https://hdl.handle.net/10993/55601

DOI
10.1186/s12920-023-01598-5

PubMed
37438803

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Abstract :

[en] Background & aims We aimed to assess the performance of European-derived polygenic risk scores (PRSs) for common metabolic diseases such as coronary artery disease (CAD), obesity, and type 2 diabetes (T2D) in the South Asian (SAS) individuals in the UK Biobank. Additionally, we studied the interaction between PRS and family history (FH) in the same population. Methods To calculate the PRS, we used a previously published model derived from the EUR population and applied it to the individuals of SAS ancestry from the UKB study. Each PRS was adjusted according to an individual’s genotype location in the principal components (PC) space to derive an ancestry adjusted PRS (aPRS). We calculated the percentiles based on aPRS and stratified individuals into three aPRS categories: low, intermediate, and high. Considering the intermediate-aPRS percentile as a reference, we compared the low and high aPRS categories and generated the odds ratio (OR) estimates. Further, we measured the combined role of aPRS and first-degree family history (FH) in the SAS population. Results The risk of developing severe obesity for SAS individuals was almost twofold higher for individuals with high aPRS than for those with intermediate aPRS, with an OR of 1.95 (95% CI = 1.71–2.23, P < 0.01). At the same time, the risk of severe obesity was lower in the low-aPRS group (OR = 0.60, CI = 0.53–0.67, P < 0.01). Results in the same direction were found in the EUR data, where the low-PRS group had an OR of 0.53 (95% CI = 0.51–0.56, P < 0.01) and the high-PRS group had an OR of 2.06 (95% CI = 2.00-2.12, P < 0.01). We observed similar results for CAD and T2D. Further, we show that SAS individuals with a familial history of CAD and T2D with high-aPRS are associated with a higher risk of these diseases, implying a greater genetic predisposition. Conclusion Our findings suggest that CAD, obesity, and T2D GWAS summary statistics generated predominantly from the EUR population can be potentially used to derive aPRS in SAS individuals for risk stratification. With future GWAS recruiting more SAS participants and tailoring the PRSs towards SAS ancestry, the predictive power of PRS is likely to improve further.

Research center :

- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

HASSANIN, Emadeldin Saeed Fathy Sayed ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core

MAY, Patrick ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core

BOBBILI, Dheeraj Reddy ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core

External co-authors :

yes

Language :

English

Title :

Assessing the performance of European-derived cardiometabolic polygenic risk scores in South-Asians and their interplay with family history

Publication date :

12 July 2023

Journal title :

BMC Medical Genomics

eISSN :

1755-8794

Publisher :

BioMed Central, London, United Kingdom

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-023-01598-5

FnR Project :

FNR16394868 - Epileptogenesis Of Genetic Epilepsies, 2021 (01/10/2021-...) - Alexander Skupin

Funders :

FNR - Fonds National de la Recherche

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since 13 July 2023

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