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

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.

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.

Metrics

  • 18,184
    views
  • 1,317
    downloads
  • 26
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Torsten Dahlén
  2. Mark Clements
  3. Jingcheng Zhao
  4. Martin L Olsson
  5. Gustaf Edgren
(2021)
An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk
eLife 10:e65658.
https://doi.org/10.7554/eLife.65658

Share this article

https://doi.org/10.7554/eLife.65658

Further reading

    1. Cancer Biology
    2. Epidemiology and Global Health
    Chelsea L Hansen, Cécile Viboud, Lone Simonsen
    Research Article

    Cancer is considered a risk factor for COVID-19 mortality, yet several countries have reported that deaths with a primary code of cancer remained within historic levels during the COVID-19 pandemic. Here, we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US. We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer, diabetes, and Alzheimer’s. Any pandemic-related changes in coding practices should be eliminated by study of MC data. Nationally in 2020, MC cancer mortality rose by only 3% over a pre-pandemic baseline, corresponding to ~13,600 excess deaths. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematological, 2–7%) than cancers with a poor survival rate (lung and pancreatic, 0–1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). To understand these differences, we simulated the expected excess mortality for each condition using COVID-19 attack rates, life expectancy, population size, and mean age of individuals living with each condition. We find that the observed mortality differences are primarily explained by differences in life expectancy, with the risk of death from deadly cancers outcompeting the risk of death from COVID-19.

    1. Epidemiology and Global Health
    Jie Liang, Yang Pan ... Fanfan Zheng
    Research Article

    Background:

    The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer.

    Methods:

    Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed.

    Results:

    A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19–1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18–1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer.

    Conclusions:

    Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases.

    Funding:

    This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466).