An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk

Dahlén, Torsten; Clements, Mark; Zhao, Jingcheng; Olsson, Martin L.; Edgren, Gustaf

doi:10.1101/2021.01.28.428569

Cited by 7 publications

(12 citation statements)

References 23 publications

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“…The distribution of blood groups, including RhD, varies globally-this may explain, at least in part, the regional differences in disease occurrence. RhD-negativity is particularly enriched in East Asian populations (28% RhD-negative) compared with European or African populations (16% and 6%, respectively) (Dahlén et al, 2021). This may reflect the different historic disease burdens on these populations.…”

Section: Discussionmentioning

confidence: 98%

“…The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.07.21264642 doi: medRxiv preprint Several association studies have found a relationship between RhD-negativity and enhanced resistance to viral infection (Flegr, 2013;Flegr, Hoffmann and Dammann, 2015;Zietz, Zucker and Tatonetti, 2020;Dahlén et al, 2021). However, systemic analysis of immune activity by RhD status had never been carried out.…”

Section: Discussionmentioning

confidence: 99%

“…Although less well studied, RhD status is also known to influence several other health outcomes (Dahlén et al, 2021). An agnostic analysis of 1217 disease states found an association between RhD status and hypertension during pregnancy (Dahlén et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

Sugrue¹,

Smith²,

Posseme

et al. 2021

Preprint

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The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of RhD on immune responses. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 30 differentially expressed genes (DEGs) between RhD-positive (n=401) and RhD-negative males (n=78). Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

Sugrue¹,

Smith²,

Posseme

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…The future studies ideally should subdivide BgA in order to comprehensively investigate the effect of high and low expressing BgA phenotypes on the risk of contracting SM. This is probably also important beyond the role of Bgs for malaria pathogenesis, as BgA has been associated to adverse outcomes also for other diseases, such as in thromboembolic diseases and more recently for COVID-19 [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes

Hedberg

Sirel²,

Moll

et al. 2021

Malar J

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Background The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria. An integral part of the severe malaria pathogenesis is rosetting, the adherence of parasite infected red blood cells (RBCs) to uninfected RBCs. Rosetting is influenced by the host’s ABO blood group (Bg) and rosettes formed in BgA have previously been shown to be more resilient to disruption by heparin and shield the parasite derived surface antigens from antibodies. However, data on rosetting in weak BgA subgroups is scarce and based on investigations of relatively few donors. Methods An improved high-throughput flow cytometric assay was employed to investigate rosetting characteristics in an extensive panel of RBC donor samples of all four major ABO Bgs, as well as low BgA expressing samples. Results All non-O Bgs shield the parasite surface antigens from strain-specific antibodies towards P. falciparum erythrocyte membrane protein 1 (PfEMP1). A positive correlation between A-antigen levels on RBCs and rosette tightness was observed, protecting the rosettes from heparin- and antibody-mediated disruption. Conclusions These results provide new insights into how the ABO Bg system affects the disease outcome and cautions against interpreting the results from the heterogeneous BgA phenotype as a single group in epidemiological and experimental studies. Graphical Abstract

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“…In later waves of the pandemic, with increasing acquired immunization possibly protecting this group of subjects, individual genetics could have played a larger role in the fatal outcome of COVID-19. Further, recent work reported that both B and Rh+ were protective against influenza due to identified zoonotic or pandemic influenza virus 37 . B was also protective against pneumonia due to S. pneumoniae.…”

Section: Namementioning

confidence: 99%

Country-Level Factors Dynamics and ABO/Rh Blood Groups Contribution To COVID-19 Mortality

Monaco

Pantaleo²,

Amoroso

et al. 2021

Preprint

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Identifying factors related to COVID-19 mortality is important to deploy effective containment measures and to safeguard categories at risk. In the last months, several investigations have tried to ascertain essential features for predicting the COVID-19 mortality tolls depending on country-specific dynamics and population structure. Most studies focused on the initial outbreak of COVID-19 spanning the first half of 2020. Several variables, including obesity, health system indicators such as hospital bed density, and bacillus Calmette-Guerin vaccination have been reported as significantly associated to COVID-19 mortality. Here, we examined in different pandemic stages some of the mentioned associations as well as ABO and Rh blood group indicators, which have also been previously linked to COVID-19 severity and fatal outcome. Using a machine learning approach, we found that the “B+” blood group frequency is an important factor at all stages of the pandemic.

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An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk

Cited by 7 publications

References 23 publications

Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes

Country-Level Factors Dynamics and ABO/Rh Blood Groups Contribution To COVID-19 Mortality

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