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The Duffy-null genotype and risk of infection

Legge, Sophie E., Christensen, Rune H., Petersen, Liselotte, Pardinas, Antonio F., Bracher-Smith, Matthew, Knapper, Steven, Bybjerg-Grauholm, Jonas, Baekvad-Hansen, Marie, Hougaard, David M., Werge, Thomas, Nordentoft, Merete, Mortensen, Preben Bo, Owen, Michael J., O'Donovan, Michael C., Benros, Michael E. and Walters, James T. R. 2020. The Duffy-null genotype and risk of infection. Human Molecular Genetics 10.1093/hmg/ddaa208
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Abstract

Many medical treatments, from oncology to psychiatry, can lower white blood cell counts and thus access to these treatments can be restricted to individuals with normal levels of white blood cells, principally in order to minimise risk of serious infection. This adversely affects individuals of African or Middle Eastern ancestries who have on average a reduced number of circulating white blood cells, due to the Duffy-null (CC) genotype at rs2814778 in the ACKR1 gene. Here, we investigate whether the Duffy-null genotype is associated with the risk of infection using the UK Biobank sample and the iPSYCH Danish case-cohort study, two population-based samples from different countries and age ranges. We found that a high proportion of those with the Duffy-null genotype (21%) had a neutrophil count below the threshold often used as a cut-off for access to relevant treatments, compared to 1% of those with the TC/TT genotype. In addition we found that despite its strong association with lower average neutrophil counts, the Duffy-null genotype was not associated with an increased risk of infection, viral or bacterial. These results have widespread implications for the clinical treatment of individuals of African ancestry and indicate that that neutrophil thresholds to access treatments could be lowered in individuals with the Duffy-null genotype without an increased risk of infection.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Oxford University Press
ISSN: 0964-6906
Date of First Compliant Deposit: 6 October 2020
Date of Acceptance: 16 September 2020
Last Modified: 26 Nov 2020 22:01
URI: http://orca-mwe.cf.ac.uk/id/eprint/135344

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