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

Nature Medicine volume 25, pages 909–910 (2019)Cite this article

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This article was retracted on 08 October 2019

Matters Arising to this article was published on 23 December 2019

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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.

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  • 08 October 2019

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

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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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Authors and Affiliations

  1. Department of Integrative Biology and Statistics, University of California, Berkeley, Berkeley, CA, USA

    Xinzhu Wei & Rasmus Nielsen

  2. Centre for GeoGenetics, University of Copenhagen, Copenhagen, Denmark

    Rasmus Nielsen

Authors
  1. Xinzhu Wei
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  2. Rasmus Nielsen
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Contributions

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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The authors declare no competing interests.

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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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Supplementary Table 1, Supplementary Materials and Supplementary Methods

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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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