Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • NEWS AND VIEWS

How rare mutations contribute to complex traits

An analysis of rare genetic variants reveals that they influence human traits through similar biological pathways to common ones. The work deepens our understanding of how this type of variant affects complex traits.
  1. Luke M. Evans

    1. Luke M. Evans is at the Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado 80303, USA, and in the Department of Ecology and Evolutionary Biology, University of Colorado Boulder.

    View author publications

    You can also search for this author in PubMed  Google Scholar

  2. Pamela N. Romero Villela

    1. Pamela N. Romero Villela is at the Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado 80303, USA, and in the Department of Psychology and Neuroscience, University of Colorado Boulder.

    View author publications

    You can also search for this author in PubMed  Google Scholar

Our understanding of the genetic mutations that affect complex human traits — such as height, smoking-related behaviour or the risk of diabetes — has been vastly broadened by genome-wide association studies (GWASs). But such research has focused largely on associations between traits of interest and variants that are common in the human population. Rare variants pose challenges to GWASs, because they can be studied using only large samples and in-depth genetic information, and can be more strongly confounded by non-genetic factors than can common variants, increasing the chance of spurious findings1. Until now, therefore, researchers have been unable to assess accurately whether rare variants contribute substantially to complex traits. Writing in Nature, Weiner et al.2 introduce a new approach to address this question. They find that, although rare variants account for a much smaller proportion of heritability than do common variants, they act through the same genes and biological pathways.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Nature 614, 418-419 (2023)

doi: https://doi.org/10.1038/d41586-023-00272-1

References

  1. Mathieson, I. & McVean, G. Nature Genet. 44, 243–246 (2012).

    Article  PubMed  Google Scholar 

  2. Weiner, D. J. et al. Nature 614, 492–499 (2023).

    Article  Google Scholar 

  3. Yang, J. et al. Nature Genet. 47, 1114–1120 (2015).

    Article  PubMed  Google Scholar 

  4. Finucane, H. K. et al. Nature Genet. 47, 1228–1235 (2015).

    Article  PubMed  Google Scholar 

  5. Bulik-Sullivan, B. et al. Nature Genet. 47, 1236–1241 (2015).

    Article  PubMed  Google Scholar 

  6. Lee, S., Abecasis, G. R., Boehnke, M. & Lin, X. Am. J. Hum. Genet. 95, 5–23 (2014).

    Article  PubMed  Google Scholar 

  7. Pasaniuc, B. & Price, A. L. Nature Rev. Genet. 18, 117–127 (2017).

    Article  PubMed  Google Scholar 

  8. The 1000 Genomes Project Consortium. Nature 526, 68–74 (2015).

    Article  PubMed  Google Scholar 

  9. The ENCODE Project Consortium et al. Nature 583, 693–698 (2020).

    Article  PubMed  Google Scholar 

  10. Mackay, T. F. C. Nature Rev. Genet. 15, 22–33 (2014).

    Article  PubMed  Google Scholar 

  11. Silventoinen, K., Kaprio, J., Lahelma, E., Viken, R. J. & Rose, R. J. Am. J. Hum. Biol. 15, 620–627 (2003).

    Article  PubMed  Google Scholar 

  12. Border, R. et al. Nature Commun. 13, 660 (2022).

    Article  PubMed  Google Scholar 

Download references

Competing Interests

The authors declare no competing interests.

Subjects

Latest on:

Nature Careers

Jobs

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing

Search

Advanced search

Quick links