CCR5-∆32 is deleterious in the homozygous state in humans

This article was retracted on 08 October 2019

A Matters Arising to this article was published on 23 December 2019

This article has been updated

Abstract

We use the genotyping and death register information of 409,693 individuals of British ancestry to investigate fitness effects of the CCR5-∆32 mutation. We estimate a 21% increase in the all-cause mortality rate in individuals who are homozygous for the ∆32 allele. A deleterious effect of the ∆32/∆32 mutation is also independently supported by a significant deviation from the Hardy–Weinberg equilibrium (HWE) due to a deficiency of ∆32/∆32 individuals at the time of recruitment.

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Fig. 1: CCR5-∆32 is deleterious in the homozygous state.

Change history

  • 08 October 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. 1.

    Normile, D. Science 362, 978–979 (2018).

    CAS  Article  Google Scholar 

  2. 2.

    Cyranoski, D. First CRISPR babies: six questions that remain Nature (30 November 2018).

  3. 3.

    Samson, M. et al. Nature 382, 722 (1996).

    CAS  Article  Google Scholar 

  4. 4.

    Wei, X. & Zhang, J. Genetics 205, 925–937 (2017).

    CAS  Article  Google Scholar 

  5. 5.

    Pavlicev, M. & Wagner, G. P. Trends Ecol. Evol. 27, 316–322 (2012).

    Article  Google Scholar 

  6. 6.

    Galvani, A. P. & Slatkin, M. Proc. Natl Acad. Sci. 100, 15276–15279 (2003).

    CAS  Article  Google Scholar 

  7. 7.

    Cahill, M. E., Conley, S., DeWan, A. T. & Montgomery, R. R. BMC Infect. Dis. 18, 282 (2018).

    Article  Google Scholar 

  8. 8.

    Joy, M. T. et al. Cell 176, 1143–1157 (2019).

    CAS  Article  Google Scholar 

  9. 9.

    Falcon, A. et al. J. Gen. Virol. 96, 2074–2078 (2015).

    CAS  Article  Google Scholar 

  10. 10.

    Mostafavi, H. et al. PLoS Biol. 15, e2002458 (2017).

    Article  Google Scholar 

  11. 11.

    Lim, J. K. & Murphy, P. M. Exp. Cell Res. 317, 569–574 (2011).

    CAS  Article  Google Scholar 

  12. 12.

    Bycroft, C. et al. Nature 562, 203 (2018).

    CAS  Article  Google Scholar 

  13. 13.

    Fry, A. et al. Am. J. Epidemiol. 186, 1026–1034 (2017).

    Article  Google Scholar 

  14. 14.

    Delgado-Rodriguez, M. & Llorca, J. J. Epidemiol. Community Health 58, 635–641 (2004).

    Article  Google Scholar 

  15. 15.

    Cox, D. R. & Oakes, D. Analysis of Survival Data (Chapman & Hall, 1984).

  16. 16.

    Nash, S et al. Progress Towards Ending the HIV Epidemic in the United Kingdom: 2018 Report (Public Health England, 2018).

  17. 17.

    Hoover, K. C. PloS ONE 13, e0204989 (2018).

    Article  Google Scholar 

  18. 18.

    Patel, V. Impact of Registration Delays on Mortality Statistics: 2016 (Office for National Statistics, 2016); https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/methodologies/impactofregistrationdelaysonmortalitystatistics2016

Download references

Acknowledgements

The authors thank D. Feehan, M. Slatkin, and P. Wilton for discussions about death rate estimation, and R. Durbin, C. Freeman, and G. McVean for discussions about UK Biobank markers. This work is supported by US National Institutes of Health (NIH) grant R01GM116044 to R.N.

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X.W. and R.N. designed the study and wrote the manuscript. X.W. analyzed the data.

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Correspondence to Xinzhu Wei or Rasmus Nielsen.

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Extended data

Extended Data Fig. 1 The deviation from HWE with age.

a, The observed deviation using age at recruitment estimated. Each dot represents one age group. The grey error bars show the 95% confidence intervals estimated from bootstrap the genotypes of individuals recruited at each age 1000 times. The sample size used for each error bar ranges from 15191 to 100117 with a mean of 65479. b, The predicted deviation from HWE using the corrected survival probability. A total of 395704 samples are used. The observed and predicted values are significantly correlated (Spearman’s correlation coefficient ρ= 0.67, P= 1.4 × 10−4).

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Wei, X., Nielsen, R. CCR5-∆32 is deleterious in the homozygous state in humans. Nat Med 25, 909–910 (2019). https://doi.org/10.1038/s41591-019-0459-6

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