1. Epidemiology and Global Health
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An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk

  1. Torsten Dahlén  Is a corresponding author
  2. Mark Clements
  3. Jingcheng Zhao
  4. Martin L Olsson
  5. Gustaf Edgren
  1. Karolinska Institutet, Sweden
  2. Lund University, Sweden
Research Article
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Cite this article as: eLife 2021;10:e65658 doi: 10.7554/eLife.65658

Abstract

Background There are multiple known associations between the ABO and RhD blood groups and disease. No systematic population-based studies elucidating associations between a large number of disease categories and blood group have been conducted.

Methods Using SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modelled outcomes for 1,217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million individuals.

Results We discovered 49 and 1 associations between a disease and ABO and RhD blood group, respectively, after adjustment for multiple testing. We identified new associations such as kidney stones and blood group B as compared to O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood group A and AB as compared to O and RhD positive as compared to negative.

Conclusion Our findings generate strong further support for previously known associations, but also indicate new interesting relations.

Funding Swedish Research Council.

Data availability

The patient level data used to construct the analyses cannot be made publicly available because of Swedish laws guarding the personal integrity of its citizens. Aggregate level data, which includes all the necessary information to recreate all the results can be requested from the authors, but requires IRB approval. This data includes subject blood group, age, sex, and calendar period, together with the corresponding number of person-years and the number of each type of event. IRB approval sought at the Swedish Ethical Review Authority (https://etikprovningsmyndigheten.se).

Article and author information

Author details

  1. Torsten Dahlén

    Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
    For correspondence
    torsten.dahlen@ki.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3856-7227
  2. Mark Clements

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Jingcheng Zhao

    Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Martin L Olsson

    Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Gustaf Edgren

    Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2198-4745

Funding

Swedish Research Council (2017-01954)

  • Gustaf Edgren

Region Stockholm clinical research appointment

  • Torsten Dahlén
  • Jingcheng Zhao
  • Gustaf Edgren

The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study has been approved by regional Stockholm County Board of Ethics Committee (ref nr: 2018/167-31). In Swedish register-based research informed consent, when involving a large number of individuals, does not need to be obtained.

Reviewing Editor

  1. David Ginsburg, Howard Hughes Medical Institute, University of Michigan, United States

Publication history

  1. Received: December 11, 2020
  2. Accepted: April 15, 2021
  3. Accepted Manuscript published: April 27, 2021 (version 1)
  4. Version of Record published: May 24, 2021 (version 2)

Copyright

© 2021, Dahlén et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Further reading

Further reading

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    Identifying the key vector and host species that drive the transmission of zoonotic pathogens is notoriously difficult but critical for disease control. We present a nested approach for quantifying the importance of host and vectors that integrates species’ physiological competence with their ecological traits. We apply this framework to a medically important arbovirus, Ross River virus (RRV), in Brisbane, Australia. We find that vertebrate hosts with high physiological competence are not the most important for community transmission; interactions between hosts and vectors largely underpin the importance of host species. For vectors, physiological competence is highly important. Our results identify primary and secondary vectors of RRV and suggest two potential transmission cycles in Brisbane: an enzootic cycle involving birds and an urban cycle involving humans. The framework accounts for uncertainty from each fitted statistical model in estimates of species’ contributions to transmission and has has direct application to other zoonotic pathogens.

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    Mohd Anisul et al.
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    Background:

    The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19.

    Methods:

    To identify host proteins that may contribute to the risk of severe COVID-19, we undertook proteome-wide genetic colocalisation tests, and polygenic (pan) and cis-Mendelian randomisation analyses leveraging publicly available protein and COVID-19 datasets.

    Results:

    Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble Fas (colocalisation probability >0.9, p=1 × 10-4), implicating Fas-mediated apoptosis as a potential target for COVID-19 risk. The polygenic (pan) and cis-Mendelian randomisation analyses showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal is highly pleiotropic, and a look-up of proteins associated with the ABO signal revealed that the strongest association was with soluble CD209. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19.

    Conclusions:

    Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.

    Funding:

    MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.