Search

Arabs account for 5% of the world population and have a high burden of cardiometabolic disease, yet clinical utility of polygenic risk prediction in Arabs remains understudied. Among 5399 Arab patients, we optimize polygenic scores for 10 cardiometabolic traits, achieving a performance that is better than published scores and on par with performance in European-ancestry individuals. Odds ratio per standard deviation (OR per SD) for a type 2 diabetes score was 1.83 (95% CI 1.74–1.92), and each SD of body mass index (BMI) score was associated with 1.18 kg/m2 difference in BMI. Polygenic scores associated with disease independent of conventional risk factors, and also associated with disease severity—OR per SD for coronary artery disease (CAD) was 1.78 (95% CI 1.66–1.90) for three-vessel CAD and 1.41 (95% CI 1.29–1.53) for one-vessel CAD. We propose a pragmatic framework leveraging public data as one way to advance equitable clinical implementation of polygenic scores in non-European populations. Arabs account for 5% of the world population and have a high burden of cardiometabolic disease. Here, the authors optimize polygenic scores for 10 cardiometabolic traits in 5399 Arabs, achieving a performance on par with that among European-ancestry individuals. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD), the leading cause of death globally, is associated with complicated underlying risk factors. We develop an artificial intelligence model to identify CVD using multimodal data, including clinical risk factors and fundus photographs from the Samsung Medical Center (SMC) for development and internal validation and from the UK Biobank for external validation. The multimodal model achieves an area under the receiver operating characteristic curve (AUROC) of 0.781 (95% confidence interval [CI] 0.766–0.798) in the SMC and 0.872 (95% CI 0.857–0.886) in the UK Biobank. We further observe a significant association between the incidence of CVD and the predicted risk from at-risk patients in the UK Biobank (hazard ratio [HR] 6.28, 95% CI 4.72–8.34). We visualize the importance of individual features in photography and traditional risk factors. The results highlight that non-invasive fundus photography can be a possible predictive marker for CVD. [ABSTRACT FROM AUTHOR]

Participation in leisure and social activities (LSA) is associated with better health outcomes and lower mortality 1-3 . Previous observational studies demonstrated a relationship between engagement in LSA and both mental and physical health 4,5 . Although several studies 6 examined the association between LSA and health outcomes, including cardiovascular disease, their possible causal relationship has not been studied. In this study, we investigated the causal relationship between LSA and various health outcomes, including cardiovascular disease, using data from genome-wide association study summary statistics (sample size = 63,926-1,557,411) and a Mendelian randomization approach. Genetically predicted LSA were associated with a reduced risk of several health outcomes, including coronary artery disease and coronary atherosclerosis. Mediation analysis indicated that these effects were partly mediated by modifiable risk factors, such as body mass index, smoking and lipid levels. These findings highlight the importance of LSA in disease prevention and health promotion., Competing Interests: Competing interests: All authors completed the International Committee of Medical Journal Editors uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ (available as Supplementary Table 19) and declare the following: W.-Y.P. is employed by a commercial company, GENINUS. P.N. reports investigator-initiated grants from Amgen, Apple, AstraZeneca, Boston Scientific and Novartis and personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Novartis and Roche/Genentech. P.N. is also a co-founder of TenSixteen Bio and a scientific advisory board member of Esperion Therapeutics, geneXwell and TenSixteen Bio and reports spousal employment at Vertex, all unrelated to the present work. R.D. reports receiving grants from AstraZeneca and grants and non-financial support from Goldfinch Bio; being a scientific co-founder, consultant and equity holder at Pensieve Health; and being a consultant for Variant Bio, all unrelated to this work. All other authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)