The Duffy-null genotype and risk of infection

Author:

Legge Sophie E1,Christensen Rune H2,Petersen Liselotte345,Pardiñas Antonio F1,Bracher-Smith Matthew1,Knapper Steven6,Bybjerg-Grauholm Jonas7,Baekvad-Hansen Marie7,Hougaard David M7,Werge Thomas8,Nordentoft Merete25,Mortensen Preben Bo345,Owen Michael J1,O’Donovan Michael C1,Benros Michael E29,Walters James T R1

Affiliation:

1. MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK

2. Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen 2605, Denmark

3. National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, 8210, Denmark

4. Centre for Integrated Register-Based Research, Aarhus University, Aarhus, 8210, Denmark

5. The Lundbeck Foundation for Integrative Psychiatric Research (iPSYCH), Aarhus University, Aarhus 8210, Denmark

6. Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK

7. Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen 2300, Denmark

8. Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde 4000, Denmark

9. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark

Abstract

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 minimize 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, because of 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 with 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 neutrophil thresholds to access treatments could be lowered in individuals with the Duffy-null genotype without an increased risk of infection.

Funder

Medical Research Council Centre

National Centre for Mental Health

Health and Care Research Wales

Independent Research Fund Denmark

Lundbeck Foundation

National Institute for Health Research

Medical Research Council

British Heart Foundation

Stanley Foundation

Simons Foundation

National Institute for Mental Health

Publisher

Oxford University Press (OUP)

Subject

Genetics(clinical),Genetics,Molecular Biology,General Medicine

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