Brief
Rare genetic variants may explain extreme human traits, study finds
Researchers at Mount Sinai report that uncommon DNA changes could have outsized effects on people at the far ends of trait distributions.
By Felo News Desk · Published
Scientists from the Icahn School of Medicine at Mount Sinai say rare genetic variants may be responsible for individuals who sit at the extreme ends of common human traits, according to a study published in Nature on Tuesday.
What happened
The research examined 74 quantitative traits—including cholesterol, blood glucose, hemoglobin, heart rate, body weight, height and age at menopause—using data from the UK Biobank and the All of Us Research Program. Researchers compared people with exceptionally high or low measurements to the broader population, looking for an enrichment of rare variants that have large biological effects.
What the reports add
The study challenges the prevailing polygenic model, which holds that thousands of common variants each contribute a tiny effect to most traits. Instead, the authors found that individuals at the far ends of a trait distribution were more likely to carry rare variants with much stronger impacts. The paper suggests that these rare variants could cluster at extremes because natural selection tends to keep strongly deleterious changes at low frequencies.
What was said
"We typically think of these traits as being shaped by thousands of genetic changes, each having a very small effect," senior corresponding author Paul O’Reilly, PhD, told ScienceTechDaily. "But our findings suggest that some people are at the ends of the trait spectrum because of a much smaller number of rare genetic variants with far stronger effects. If we can identify who these people are, clinicians may be able to offer them preventive care or treatments better suited to their genetic risk profile."
How it came about
The analysis built on earlier genome‑wide association studies that mapped common variants for many traits. By leveraging the large, diverse cohorts of the UK Biobank and the All of Us Research Program, the team could detect the influence of rarer alleles that were previously invisible in smaller samples.
Key facts
- The study examined 74 quantitative traits. (scitechdaily.com)
- Data were drawn from the UK Biobank and the All of Us Research Program. (scitechdaily.com)
- Rare variants were found to be more common among individuals at trait extremes. (scitechdaily.com)
- The research was published in the journal Nature. (scitechdaily.com)
- Paul O’Reilly is senior corresponding author and professor at Mount Sinai. (scitechdaily.com)
Sources
- [1] scitechdaily.com — originally reported as “Extreme Human Traits May Have a Simple Genetic Explanation”
