Polygenic Risk Scores for Cardio-renal-metabolic Diseases in the Penn Medicine Biobank
Kember, R.; Verma, A.; Verma, S. S.; Lucas, A.; Judy, R.; Chen, J.; Damrauer, S.; Rader, D. J.; Ritchie, M. D.
Show abstract
Cardio-renal-metabolic (CaReMe) conditions are common and the leading cause of mortality around the world. Genome-wide association studies have shown that these diseases are polygenic and share many genetic risk factors. Identifying individuals at high genetic risk will allow us to target prevention and treatment strategies. Polygenic risk scores (PRS) are aggregate weighted counts that can demonstrate an individuals genetic liability for disease. However, current PRS are often based on European ancestry individuals, limiting the implementation of precision medicine efforts in diverse populations. In this study, we develop PRS for six diseases and traits related to cardio-renal-metabolic disease in the Penn Medicine Biobank. We investigate their performance in both European and African ancestry individuals, and identify genetic and phenotypic overlap within these conditions. We find that genetic risk is associated with the primary phenotype in both ancestries, but this does not translate into a model of predictive value in African ancestry individuals. We conclude that future research should prioritize genetic studies in diverse ancestries in order to address this disparity.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential for early cardiovascular disease intervention 95%
- Inclusion of Variants Discovered from Diverse Populations Improves Polygenic Risk Score Transferability 95%
- Evaluating Genomic Polygenic Risk Scores for Childhood Acute Lymphoblastic Leukemia in Latinos 94%
Similar papers in this journal
- GWAS in Africans identifies novel lipids loci and demonstrates heterogenous association within Africa 95%
- The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: A Mendelian randomization study 94%
- Using human genetics to understand the causes and consequences of circulating cardiac troponin I in the general population 94%
Similar papers in this journal
- A Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization 96%
- Machine Learning to Understand Genetic and Clinical Factors Associated with the Pulse Waveform Dicrotic Notch 94%
- Coronary Artery Disease Risk of Familial Hypercholesterolemia Genetic Variants Independent of Historical Cholesterol Exposure 94%
Similar papers in this journal
- Genetic association studies using disease liabilities from deep neural networks 95%
- Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity 95%
- Characterization of exome variants and their metabolic impact in 6,716 American Indians from Southwest US 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.