AI Article Synopsis
- * Rare mutations in certain genes have a much stronger impact on severe diseases than more common genetic variations.
- * By using rare variants to create a genetic risk model, we were able to predict disease risk more effectively across different populations compared to traditional methods that rely on common variants.
Article Abstract
Unlabelled: We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases and observed that rare, penetrant mutations in genes implicated by genome-wide association studies confer ∼10-fold larger effects than common variants in the same genes. Consequently, an individual at the phenotypic extreme and at the greatest risk for severe, early-onset disease is better identified by a few rare penetrant variants than by the collective action of many common variants with weak effects. By combining rare variants across phenotype-associated genes into a unified genetic risk model, we demonstrate superior portability across diverse global populations compared to common variant polygenic risk scores, greatly improving the clinical utility of genetic-based risk prediction.
One Sentence Summary: Rare variant polygenic risk scores identify individuals with outlier phenotypes in common human diseases and complex traits.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187340 | PMC |
| http://dx.doi.org/10.1101/2023.05.01.23289356 | DOI Listing |
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