Overview
- The paper, published in Nature on May 27, 2026, reports that people at the very high or very low ends of many traits are often enriched for a small number of rare genetic variants with large effects.
- Researchers used two complementary methods—a population-level genetic analysis and comparisons between siblings—to test whether trait extremes have a different genetic architecture than the general population.
- The team analyzed 74 quantitative traits, including cholesterol, blood glucose, height and age at menopause, using large datasets such as the UK Biobank and the All of Us Research Program.
- Authors say the findings open the possibility of identifying individuals whose extreme traits stem from rare variants for more tailored care, but they stress the need for replication, functional follow-up and study of environmental and ancestry effects.
- The work was motivated by evolutionary reasoning that selection keeps large-effect, harmful variants rare, and the authors plan further studies to map the specific variants and assess clinical usefulness and generalizability.