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.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Normile, D. Science 362, 978–979 (2018).
Cyranoski, D. First CRISPR babies: six questions that remain Nature (30 November 2018).
Samson, M. et al. Nature 382, 722 (1996).
Wei, X. & Zhang, J. Genetics 205, 925–937 (2017).
Pavlicev, M. & Wagner, G. P. Trends Ecol. Evol. 27, 316–322 (2012).
Galvani, A. P. & Slatkin, M. Proc. Natl Acad. Sci. 100, 15276–15279 (2003).
Cahill, M. E., Conley, S., DeWan, A. T. & Montgomery, R. R. BMC Infect. Dis. 18, 282 (2018).
Joy, M. T. et al. Cell 176, 1143–1157 (2019).
Falcon, A. et al. J. Gen. Virol. 96, 2074–2078 (2015).
Mostafavi, H. et al. PLoS Biol. 15, e2002458 (2017).
Lim, J. K. & Murphy, P. M. Exp. Cell Res. 317, 569–574 (2011).
Bycroft, C. et al. Nature 562, 203 (2018).
Fry, A. et al. Am. J. Epidemiol. 186, 1026–1034 (2017).
Delgado-Rodriguez, M. & Llorca, J. J. Epidemiol. Community Health 58, 635–641 (2004).
Cox, D. R. & Oakes, D. Analysis of Survival Data (Chapman & Hall, 1984).
Nash, S et al. Progress Towards Ending the HIV Epidemic in the United Kingdom: 2018 Report (Public Health England, 2018).
Hoover, K. C. PloS ONE 13, e0204989 (2018).
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
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.
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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).
About this article
Cite this article
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
This article is cited by
Assessing efficiency of fine-mapping obesity-associated variants through leveraging ancestry architecture and functional annotation using PAGE and UKBB cohorts
Human Genetics (2023)
CCR5-Δ32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool
Cell & Bioscience (2020)
Journal of Molecular Evolution (2020)
Journal of Molecular Evolution (2020)