Rare penetrant mutations confer severe risk of common diseases

Science(2023)

引用 18|浏览46
暂无评分
摘要
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 similar to 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 with common-variant polygenic risk scores, greatly improving the clinical utility of genetic-based risk prediction.
更多
查看译文
关键词
rare penetrant mutations,common diseases,severe risk
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络