Science journal retracts article linking CCR5 deletion to reduced life expectancy
18 October 2019. Related: Basic science and immunology.
Richard Jefferys, TAG
In June 2019, a short paper was published in the journal Nature Medicine reporting that individuals homozygous for the CCR5-∆32 mutation showed a 21% increase in the rate of all-cause mortality compared to those without the mutation (or heterozygotes, who inherit the mutation from one parent). [1]
The senior author, Rasmus Nielsen, stated to the Wall Street Journal that this would equate to a nearly two-year shortening of lifespan on average. [2]
The findings were the subject of hundreds of media articles, largely because they came on the heels of a misguided and completely unethical experiment in which the CCR5 gene was edited in two embryos, leading to the birth of genetically altered twins. [3]
Questions were also raised about possible relevance to HIV cure research studies that attempt to ablate CCR5 expression with gene therapies. [4]
Yesterday, Nature Medicine published a notice that the paper has been retracted. [5]
News that the retraction was imminent emerged two weeks ago in an article by Rebecca Robbins for STAT News, after Nielsen tweeted an acknowledgement that a major error had been found. [7]
The original analysis was based on data from the UK Biobank, and it turned out that a technical artifact meant that individuals homozygous for the CCR5-∆32 mutation were underrepresented in the data (the problem is outlined in a paper available on the bioRxiv preprint server). [8]
These developments do not necessarily mean that homozygosity for the CCR5-∆32 mutation is entirely benign; a number of published reports have suggested an association with impaired responses to certain infectious diseases (particularly West Nile Virus, and possibly influenza as well). [9, 10]
Also, previously unappreciated roles of the CCR5 receptor continue to be identified, such as the promotion of hematopoietic stem and progenitor cell regeneration after radiation treatment. [11] But, after this retraction, there is no evidence (at least as yet) that any negative effects of the CCR5-∆32 mutation add up to a reduced life expectancy for homozygous individuals.
Source
Jefferys R. Widely publicised report associating the CCR5-Δ32 mutation with reduced longevity is retracted. TAB Basic Science Blog. (09 Oct 2019).
https://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2019/10/widely-publicized-report-associating-the-ccr5-%CE%B432-mutation-with-reduced-longevity-is-retracted.html
References
- Wei X, Nielsen R. CCR5-∆32 is deleterious in the homozygous state in humans. Brief Communication. Nature 2019: 25; 909–910 (03 June 2019).
https://www.nature.com/articles/s41591-019-0459-6 - Rana P. Study of HIV-related mutation adds to worries about first gene-edited babies (05 June 2019).
https://www.wsj.com/articles/study-of-hiv-related-mutation-adds-to-worries-about-first-gene-edited-babies-11559646973 - Jeffery R. Treatment Action Group statement on the reported birth of twins with edited CCR5 genes. TAG Blog. (26 November 2018).
http://www.treatmentactiongroup.org/content/treatment-action-group-statement-reported-birth-twins-edited-ccr5-genes - Sax P. Exploiting the CCR5 Receptor: Potential Avenue for HIV Cure?Medscape. Commentary. (19 July 2019).
https://www.medscape.com/viewarticle/915384 - Wei X, Nielsen R. Retraction Note: CCR5-∆32 is deleterious in the homozygous state in Nature Medicine (2019).
https://www.nature.com/articles/s41591-019-0637-6 - Robbins R. STAT News. Major error undermines study suggesting change introduced in the CRISPR babies experiment shortens lives. (27 September 2019).
https://www.statnews.com/2019/09/27/major-error-undermines-study-suggesting-change-introduced-in-the-crispr-babies-experiment-shortens-lives - Nielsen R. “The one thing that all scientists fear the most is to find out that a major result they have published was based on erroneous data. This is an event that will affect you for the rest of your scientific career.” Twitter. (21 September 2019).
https://twitter.com/ras_nielsen/status/1177635229768372224 - Maier R. No statistical evidence for an effect of CCR5-Δ32 on lifespan in the UK Biobank cohort. ObioRxiv preprint server. (02 Oct 2019).
https://www.biorxiv.org/content/10.1101/787986v1 - Glass WG et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. JEM 203 (1): 35 (17 January 2006)
http://jem.rupress.org/content/203/1/35.long - Falcon A et al. CCR5 deficiency predisposes to fatal outcome in influenza virus infection. Jour Gen Viro 96 (8). ()1 August 2015).
https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.000165 - Piryani SO et al. CCR5 signaling promotes murine and human hematopoietic regeneration following ionizing radiation. Stem Cell Reports. 13 (1);76-90. (09 July 2019).
https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(19)30145-6