Genetically Determined ABO Blood Group and its Associations With Health and Disease
Arteriosclerosis, Thrombosis, and Vascular Biology
Graphical Abstract
Abstract
Objective:
To determine the spectrum of phenotypes linked to the ABO blood group system, using genetic determinants of the ABO blood group system.
Approach and Results:
We assessed the risk of 41 health and disease outcomes, and 36 linear traits associated with the ABO blood group system in the UK Biobank cohort. A total of 406 755 unrelated individuals were included in this study. Blood groups A, B, and O were determined based on allele combinations of previously established single-nucleotide polymorphisms rs8176746, rs8176719 in the ABO gene. Group AB was excluded because of its relative small sample size. Overall, 187 387 (46%) were male with a mean (SD) age of 57±8.1 years and a median total exposure of 64 person-years (interquartile range, 57–70). Of 406 755 individuals, 182 621 (44.9%) participants had blood group O, 182 786 (44.9%) had blood group A, and 41 348 (10.2%) had blood group B. ABO blood groups were associated with 11 health and disease outcomes (P<2.19×10−4). ABO blood groups were primarily associated with cardiovascular outcomes. Compared with individuals with blood group O, blood groups A and B were associated with increased odds of up to 1.56 (95% CI, 1.43–1.69) for thromboembolic events and decreased odds for hypertension (0.94 [95% CI, 0.92–0.97]).
Conclusions:
The ABO blood group system is associated with several parameters of healthy aging and disease development. Knowledge of ABO blood groups might be of interest for more personalized approaches towards health maintenance and the prevention of diseases.
Highlights
•
The ABO blood group system has been linked to several diseases.
•
However, a phenome-wide scan to assess the extent of these associations has not been performed yet.
•
The ABO blood group system was associated with healthy aging and disease development.
•
ABO blood groups were primarily associated with cardiovascular outcomes.
•
The determination of ABO blood groups could serve in blood group individualized approaches towards health maintenance and prevention of diseases.
Introduction
The ABO blood group system was discovered by the Austrian pathologist Karl Landsteiner in 1901, who classified the blood groups based on the presence of A and B antigens on the surface of red blood cells after noting patterns of agglutination during blood transfusions.1 Since the discovery of the ABO blood group system, several studies investigating the relationship between the ABO blood group system and various diseases have been conducted.2 One of the discovered relationships is the association between ABO blood groups and blood coagulation.3–5 Individuals with non-O blood groups demonstrate an increased risk for several thromboembolic diseases, including ischemic heart disease, pulmonary thromboembolism (PE), and deep vein thrombosis.2,6 The associations between ABO blood group with thromboembolic diseases and bleeding risk are possibly mediated not only by the relationship between glycosyltransferase activity but also via plasma levels and biologic activity of VWF (von Willebrand factor), a carrier protein for coagulation factor VIII, which is reduced in O-group individuals.3,7,8 In O-group individuals, reduced risks of thromboembolic diseases have been reported, although with regards to bleeding risk, its correlation with reduced VWF levels remains inconclusive.5,9,10 The expression of A or B antigens, and thereby an individual’s blood group, is the result of allelic combinations of genetic variants in the ABO gene on chromosome 9 (9q34.2).5,11,12 In agreement with studies which used the ABO phenotype, genetically determined non-O blood groups were similarly associated with an increased risk of ischemic stroke and venous thromboembolism.5 However, these studies included only a small number of participants or were limited to one disease. Furthermore, most studies studied differences between blood group O and non-O, rather than studying blood group A, B, and AB separately.2,5,13–16 The association between blood group and healthy aging remains unknown as well. Therefore, we aimed to genetically determine ABO blood groups in 406 755 individuals and provide a phenome-wide overview of the associations between ABO blood groups with prevalent and new-onset disease, as well as health in the UK Biobank.
Materials and Methods
The data that support the findings of this study are available in the UK Biobank study.
UK Biobank Participants
The UK Biobank study design and population have been described in detail elsewhere.17 In brief, UK Biobank is a large community-based prospective study in the United Kingdom that recruited >500 000 participants aged 40 to 69 years old with the aim of improving prevention, diagnosis, and treatment of a plethora of illnesses including cancer, diabetes mellitus, stroke, and heart diseases. All participants gave informed consent for the study. UK Biobank has approval from the relevant institutional review boards, namely, the North West Multi-Center Research Ethics Committee for the United Kingdom, from the National Information Governance Board for Health and Social Care for England and Wales, and from the Community Health Index Advisory Group for Scotland.18 The present study was conducted under application number 15 031 of the UK Biobank resource. The data from the UK Biobank resource are available for other researchers following an approved research proposal.19
Genotyping and Imputation
The genotyping process and arrays used in the UK Biobank study have been described elsewhere in more detail.18 Briefly, participants were genotyped using the custom UK Biobank Lung Exome Variant Evaluation Axiom (Affymetrix; n=49 949), which includes 807 411 single-nucleotide polymorphisms (SNPs) or the custom UK Biobank Axiom array (Affymetrix; n=452 713), which includes 820 967 SNPs (5). The arrays have insertion and deletion markers with >95% common content.18,20 Imputed genotype data were provided by UK Biobank, based on merged UK10K and 1000 Genomes phase 3 panels.21 Participants were excluded if there was no genetic data available or if there was a mismatch between genetic and reported sex (n=378). Furthermore, participants with high missingness, excess heterozygosity, or familial relatedness were excluded (n=963). Last, we excluded participants of whom we could not create blood group based on the allelic combinations in previous literature (unknown blood group), or who had blood group AB (n=15 529). The latter were excluded due to their very small sample size compared with the other blood groups (A, B, and O). We created a maximal independent set of 406 755 unrelated individuals with available information on blood group. Figure 1 shows a flowchart of the study sample selection.
ABO Determination
ABO blood group was determined using allele combinations of SNP rs8176746 and rs8176719 located in the ABO gene (Figure 2).11 Alleles were matched according to previous literature, based on frequency.11 Table I in the online-only Data Supplement contains a detailed list of the extracted SNPs. Information on blood groups A, B, and O was available for 406 755 participants.
Definition of Prevalent and New-Onset Disease and (Cardiovascular) Health
We studied the association with ABO in 41 phenotypes and 36 linear traits. Definitions used to define incident and prevalent outcomes are presented in Table II in the online-only Data Supplement. We used self-reported diagnoses and medication, and Hospital Episode Statistics data, as previously described.22 Furthermore, 2 health variables were generated. Cardiovascular health was defined as the absence of diabetes mellitus, stroke, and myocardial infarction.23 Total health was based on the World Health Organization’s top 10 causes of deaths in high-income countries and defined as absence of coronary artery disease, stroke, Alzheimer disease, lung cancer, chronic obstructive pulmonary disorder, pneumonia, colon cancer, rectal cancer, diabetes mellitus, kidney diseases, and breast cancer before inclusion or during follow-up.24 Follow-up for disease outcomes was censored on March 31, 2015, for participants from England, August 31, 2014, for participants from Scotland, and on February 28, 2015, for participants from Wales. Follow-up for death was from inclusion until January 31, 2016, for participants from England and Wales and until November 30, 2015, for participants from Scotland.
Vital Signs, Blood Count, and Longevity
At the baseline visit, vital signs and biological samples were collected, together with data of self-completed questionnaires, interviews, and physical measurements. Blood pressure was measured twice, automated or manually, and average values were used. Automated measurements were corrected as proposed by Stang et al.25 Longevity was based on parental lifespan (field ID 1807 and 3526).
Statistical Analysis
We excluded outcomes with a prevalence of 1% or less from the analyses. Logistic regression analyses were performed to assess the effect of blood group on combined previous and new-onset disease outcomes. Odds ratios (ORs) with 95% CI and standardized beta (β) were calculated between blood groups (A versus O [reference], B versus O [reference], and A versus B [reference]), and non-O versus O (reference). Logistic regression analyses were adjusted for age at moment of last follow-up, sex, genotyping chip, and the first 30 principal components (to adjust for population structure) provided by UK Biobank. Furthermore, Cox regression analyses were performed for the significant associations found in the logistic regression analyses, adjusted for age at moment of last follow-up, sex, genotyping chip, and the first 30 principal components. The time frame used for the Cox regression analyses was from birth until last follow-up. Linear regression analyses were performed to assess the effect of blood group on anthropometric measurements, hemodynamics, laboratory measurements, longevity, and pulmonary function at baseline. Linear regression analyses were adjusted for age at baseline visit, sex, genotyping chip, and the first 30 principal components. We considered a 2-sided P<2.19×10−4 (P<0.05 divided by the number of independent tests, calculated using the Galwey method, ie, 0.05/228) statistically significant for all analyses.26 We tested for interactions between blood group and risk factors of thrombosis (sex, body mass index, smoking, cancer, oral contraceptive use, and menopause27) on the outcome of thrombosis. We considered a P value of 0.05 as statistical significant for interaction. All analyses were performed using Stata version 15.
Results
Population Characteristics
From the 502 559 individuals with available genotype, we included a total of 406 755 individuals for the present analyses (Figure 1). Participants with blood group AB (n=15 529 [3.7%]) were excluded because of the small sample size in comparison with blood groups O (n=182 621 [44.9%]), A (n=182 786 [44.9%]), and B (n=41 348 [10.2%]; Table 1). Overall, 187 387 (46%) were male with a mean age of 57±8.1 years and a median total exposure of 64 person-years (interquartile range, 57–70). Baseline characteristics, including the most common diseases in medical history and during up to 7 years (median 6 years [interquartile range, 5–7]) of follow-up, are provided in Table 1. All-cause mortality, cardiovascular mortality, and mortality due to cancer are shown per age group of 5 years (Table 2).
| O (n=182 621) | A (n=182 786) | B (n=41 348) | |
|---|---|---|---|
| Male | 84 460 (46.2%) | 83 885 (45.9%) | 19 033 (46.0%) |
| Age, mean (SD), y | 57.0 (8.1) | 57.1 (8.1) | 56.5 (8.2) |
| Years of exposure, median (IQR), y | 64.3 (56.6–69.8) | 64.5 (56.8–69.8) | 63.6 (55.9–69.3) |
| Smoking behavior | |||
| Never or <100 cigarettes | 100 351 (56.4%) | 100 419 (56.4%) | 23 553 (58.6%) |
| Stopped >12 mo | 57 325 (32.2%) | 57 780 (32.5%) | 12 037 (29.9%) |
| Stopped ≤12 mo | 888 (0.5%) | 807 (0.5%) | 207 (0.5%) |
| Active occasionally | 4989 (2.8%) | 4908 (2.8%) | 1210 (3.0%) |
| Active daily | 14 351 (8.1%) | 14 061 (7.9%) | 3196 (7.9%) |
| Body mass index, kg/m2 | 27.4 (4.8) | 27.4 (4.8) | 27.4 (4.86) |
| Hyperlipidemia | 39 189 (21.5%) | 41 633 (22.8%) | 9188 (22.2%) |
| Statin use | 30 311 (16.6%) | 32 466 (17.8%) | 7051 (17.1%) |
| Nonstatin lipid lowering medication | 2217 (1.2%) | 2402 (1.3%) | 525 (1.3%) |
| Cholesterol, mmol/L | 5.7 (1.1) | 5.7 (1.2) | 5.6 (1.1) |
| HDL, mmol/L | 1.4 (0.4) | 1.5 (0.4) | 1.4 (0.4) |
| LDL, mmol/L | 3.5 (0.9) | 3.6 (0.9) | 3.5 (0.9) |
| Triglycerides, mmol/L | 1.5 (1.0–2.2) | 1.5 (1.0–2.1) | 1.5 (1.0–2.2) |
HDL indicates high-density lipoprotein; IQR, interquartile range; and LDL, low-density lipoprotein.
| Age Category | <45 y | 45–49 | 50–54 | 55–59 | 60–64 | 65–69 | ≥70 y | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Blood Group | O | A | B | O | A | B | O | A | B | O | A | B | O | A | B | O | A | B | O | A | B |
| Number | 18 651 | 18 308 | 4766 | 24 564 | 23 902 | 5748 | 27 768 | 27 759 | 6628 | 32 891 | 32 856 | 7411 | 43 824 | 44 717 | 9439 | 33 811 | 34 204 | 7140 | 1112 | 1040 | 216 |
| All cause | 130 (0.7%) | 126 (0.7%) | 30 (0.6%) | 257 (1.0%) | 257 (1.1%) | 60 (1.0%) | 451 (1.6%) | 439 (1.6%) | 119 (1.8%) | 800 (2.4%) | 793 (2.4%) | 165 (2.2%) | 1575 (3.6%) | 1532 (3.4%) | 338 (3.6%) | 1926 (5.7%) | 1919 (5.6%) | 412 (5.8%) | 82 (7.4%) | 87 (8.4%) | 13 (6.0%) |
| Cardiovascular | 16 (0.1%) | 17 (0.1%) | 9 (0.2%) | 55 (0.2%) | 54 (0.2%) | 10 (0.2%) | 82 (0.3%) | 70 (0.3%) | 15 (0.2%) | 138 (0.4%) | 177 (0.5%) | 34 (0.5%) | 311 (0.7%) | 354 (0.8%) | 75 (0.8%) | 445 (1.3%) | 413 (1.2%) | 91 (1.3%) | 18 (1.6%) | 15 (1.4%) | 1 (0.5%) |
| Cancer (malignant) | 70 (0.4%) | 58 (0.3%) | 8 (0.2%) | 119 (0.5%) | 140 (0.6%) | 23 (0.4%) | 269 (1.0%) | 270 (1.0%) | 77 (1.2%) | 475 (1.4%) | 469 (1.4%) | 101 (1.4%) | 951 (2.2%) | 875 (2.0%) | 187 (2.0%) | 1102 (3.3%) | 1091 (3.2%) | 235 (3.3%) | 44 (4.0%) | 55 (5.3%) | 11 (5.1%) |
Disease
The significant associations of the different blood groups with 34 independent clinical outcomes and 23 linear traits are shown in Figures 3 and 4. The prevalence rates of the clinical outcomes associated with blood groups are shown in Table III in the online-only Data Supplement. Full details of the associations are presented in Tables IV and V in the online-only Data Supplement. Associations with blood group AB are attached as supplementary information (Table VI in the online-only Data Supplement). The observed associations with traits and disease outcomes differed per blood group and for combined non-O blood groups, that is, blood group A or B.
Individuals with non-O blood groups, that is, blood group A or B, were at up to 1.6 times (OR, 1.56 [95% CI, 1.43–1.69]) higher risk of thromboembolic events, compared with individuals with blood group O. They had a nominally lower risk of gastrointestinal bleeding compared with individuals with blood group O, although not statistically significant (OR, 0.95 [95% CI, 0.91–0.99]). Non-O blood groups were also associated with a lower risk of hypertension compared with blood group O (OR, 0.97 [95% CI, 0.95–0.98]; and OR, 0.94 [95% CI, 0.92–0.97], for blood group A and B, respectively; Figure 3).
Blood group A was associated with a higher risk of heart failure (OR, 1.14 [95% CI, 1.07–1.21]), atherosclerosis (OR, 1.05 [95% CI, 1.03–1.08]), hyperlipidemia (OR, 1.09 [95% CI, 1.07–1.11]) compared with blood group O (Figure 3). Additionally, blood group A was associated with a higher risk of atopy (OR, 1.03 [95% CI, 1.01–1.04)] compared with blood group O. Compared with blood group B, blood group A was associated with an increased risk of hyperlipidemia (OR, 1.08 [95% CI, 1.04–1.11]) and an increased risk of sleep apnea (OR, 1.23 [95% CI, 1.08–1.39]; Figure 3). There was no appreciable change in risk associated with other outcomes.
In addition to an increased risk of thromboembolic diseases and hypertension, blood group B was associated with an increased risk of myocardial infarction in comparison to blood group O (OR, 1.13 [95% CI, 1.06–1.20]; Figure 3).
No associations were observed between the different blood groups and cancer.
The significant associations between ABO blood group and diseases remained significant after cox regression analysis (Table 3).
| HR | 95% CI | P Value | |
|---|---|---|---|
| Non-O vs O | |||
| Atherosclerosis | 1.05 | 1.03–1.07 | 5.90×10−6 |
| Heart failure | 1.10 | 1.04–1.16 | 4.16×10−4 |
| Hypertension | 0.97 | 0.96–0.98 | 2.10×10−7 |
| Hyperlipidemia | 1.08 | 1.06–1.10 | 5.20×10−13 |
| Myocardial infarction | 1.08 | 1.05–1.12 | 4.03×10−6 |
| Thrombosis | 1.44 | 1.39–1.50 | 2.02×10−89 |
| Deep venous thrombosis | 1.51 | 1.44–1.59 | 5.29×10−66 |
| Pulmonary embolism | 1.47 | 1.39–1.55 | 1.46×10−43 |
| Thromboembolism | 1.44 | 1.37–1.51 | 2.53×10−46 |
| A vs O | |||
| Atherosclerosis | 1.05 | 1.03–1.07 | 3.47×10−5 |
| Heart failure | 1.11 | 1.05–1.18 | 1.99×10−4 |
| Hypertension | 0.98 | 0.97–0.99 | 6.07×10−5 |
| Hyperlipidemia | 1.09 | 1.07–1.12 | 3.08×10−16 |
| Thrombosis | 1.44 | 1.39–1.50 | 3.05×10−82 |
| Deep venous thrombosis | 1.50 | 1.43–1.58 | 1.37×10−59 |
| Pulmonary embolism | 1.48 | 1.40–1.57 | 2.02×10−42 |
| Thromboembolism | 1.44 | 1.37–1.52 | 7.28×10−44 |
| B vs O | |||
| Hypertension | 0.95 | 0.93–0.97 | 1.29×10−7 |
| Myocardial infarction | 1.15 | 1.08–1.21 | 2.14×10−6 |
| Thrombosis | 1.45 | 1.37–1.54 | 1.68×10−34 |
| Deep venous thrombosis | 1.55 | 1.44–1.68 | 3.64×10−29 |
| Pulmonary embolism | 1.42 | 1.28–1.54 | 3.34×10−13 |
| Thromboembolism | 1.42 | 1.30–1.54 | 2.04×10−16 |
| A vs B | |||
| Hyperlipidemia | 1.08 | 1.04–1.12 | 1.43×10−5 |
HR indicates hazard ratio.
Healthy Aging
We investigated the association between blood groups with cardiovascular and total health and found non-O individuals had worse cardiovascular and total health and reduced longevity compared with individuals with blood group O (OR, 0.95 [95% CI, 0.92–0.97]; OR, 0.97 [95% CI, 0.96–0.99]; β, −0.03 [95% CI, −0.05 to −0.02]). More specifically, this was seen in individuals with blood group A compared with individuals with blood group O (cardiovascular health: OR, 0.95 [95% CI, 0.93–0.97]; total health: OR, 0.97 [95% CI, 0.96–0.99]; β, −0.03 [95% CI, −0.05 to −0.02], respectively; Tables III and IV in the online-only Data Supplement). No differences in cardiovascular or total health, nor in longevity were observed between blood group A and B or between B and O.
Interactions of Blood Group and Risk Factors for Thrombosis Diseases
We studied possible interactions between blood groups and known risk factors for thrombosis (sex, body mass index, smoking, cancer, oral contraceptives, and menopause27). A significant interaction was observed for sex and blood group. Within blood groups A and B, men had higher odds for developing thrombosis, deep vein thrombosis, and PE compared with men with blood group O (Table VII in the online-only Data Supplement). Within blood group A, individuals with a medical history of cancer had lower odds for developing thrombosis, thromboembolism, or PE, compared with individuals with blood group O. A similar phenomenon was observed when blood groups A and B were combined. Within blood group A, women in menopause had lower odds for developing thrombosis, deep vein thrombosis, thromboembolism, or PE compared with women in menopause with blood group O.
Discussion
In this large community-based population, we determined ABO blood group phenotypes based on inherited allelic combinations and observed numerous associations between the ABO blood group system with healthy aging and the development of a multitude of diseases. The ABO blood groups were primarily associated with cardiovascular outcomes. The present study observed that individuals with blood group A and B were at higher risk of developing thromboembolic diseases, but lower risk of hypertension, when compared with O-group individuals. Individuals with blood group A were at higher risk of developing hyperlipidemia, atherosclerosis, and heart failure compared with blood group O, whereas individuals with blood group B were at higher risk of myocardial infarction compared with individuals with blood group O. The observed differences suggest blood group-specific approaches for the maintenance of human health and the prevention and treatment of a multitude of diseases.
ABO and Disease
Our results are concordant with previous smaller observational reports suggesting an increased risk of thromboembolic events in non-O blood group individuals compared to individuals with blood group O.28 In both blood groups A and B, we observed similar increased risks of developing thromboembolic events compared with blood group O. Interestingly, we did not observe the same effects on blood cell characteristics between individuals with blood group A or B compared to blood group O. Because thrombosis is a well-balanced and complex process, which is affected by a plethora of factors, there could be different biological mechanisms (ie, cell functionality, number of cell receptors) involved in the increased risk of thromboembolic events in blood group A and blood B individuals, besides the already established relation with VWF.9 Molecular studies are necessary to further unravel these differences between blood group A and blood group B. Nevertheless, this study provides an elegant overview for future research possibilities. In addition, it might be of interest to take sex differences into account because we observed interactions between sex and blood groups in the development of thromboembolic disease.
Our analyses indicated an increased risk of hyperlipidemia in individuals with blood group A compared to both blood group O as well as blood group B, which is also in line with previous studies. Earlier research has associated blood group A with higher total cholesterol levels as well as low-density lipoprotein cholesterol compared with both blood groups B and O.29 However, in a study including 6476 individuals with Asian backgrounds, cholesterol levels were increased in individuals with blood group A or B compared to blood group O but not higher in individuals with A compared to B.13 The difference in outcomes between this study in Asians and our study might be because of the larger sample size of our study (66× larger). Whether epigenetic factors play a role in these differences remains to be investigated. In addition, previous reports have also shown that non-O blood group patients affected by familial hypercholesterolemia were at a 2-fold increased risk of cardiovascular diseases compared with O blood group patients.30
Interactions Between ABO Blood Group and Risk Factors for Thromboembolic Diseases
The present study provides information on the sex differential for thromboembolic diseases in the context of ABO blood group in the general population. The interaction between blood group and sex has been previously observed in patients with persistent antiphospholipid antibodies.31 We did not find an interaction with use of contraceptive medication. This might be explained due to the small number of women (<1%) still using contraceptive medication in this group of middle-aged women from the UK Biobank (median age when quitted oral contraceptives was 30 years [interquartile range, 24–35 years). Of interest is the interaction between blood group and cancer. Previous literature reported non-O blood groups to be a risk factor for venous thromboembolism in adult patients with malignant gliomas and children with acute lymphoblastic leukemia.32,33 Also in the Longitudinal Investigation of Thromboembolism Etiology study, an increased risk of venous thromboembolism due to cancer was observed in non-O individuals compared with individuals with blood group O.34 The present analyses add to these previous findings, indicating individuals with blood group O and a medical history of cancer had higher odds of developing thrombosis, thromboembolism or PE compared with blood group A or A + B combined. Although the mechanism underlying the interaction between blood group and cancer requires further research, the ABO blood group might play a role in counseling, risk stratification and thromboprophylaxis in individuals with cancer.
ABO and Healthy Aging
We also investigated whether specific blood groups were associated with cardiovascular and total health. Individuals with blood group A had worse perspectives for healthy aging compared with individuals with blood group O. No associations were observed between blood group B versus O, suggesting the association may be specific for blood group A and not non-O blood groups in general. Another explanation could be the small sample size of blood group B compared with blood group A and blood group O. Our finding is in line with previous literature and indicates potential implications for the maintenance of health and prevention of diseases in different blood groups within the ABO system.34 Individuals with blood group A may benefit from early preventive interventions to reduce their risk of poor cardiovascular or total health.
Strengths and Limitations
The major strengths of this study were the large sample size, variety of examined traits and disease outcomes, adjustment for multiple covariates, and the prospective design of the UK Biobank. However, this study has some limitations. We excluded individuals with blood group AB from our main analysis because of the relative large difference in sample size compared with blood group O, A, and B. We included this information in the online-only Supplement Data. Nevertheless, in contrast to previous studies, we were able to study individuals with blood groups A and B separately rather than only as a combined non-O group. A second limitation was that we were not able to take into account the possible role of the Rhesus and other blood group systems, which could provide other and more detailed insights. Furthermore, we determined the ABO phenotype based on previously reported SNP allele combinations, but because blood group has not been determined in UK Biobank blood samples, comparison of the genetically determined phenotype and laboratory determined phenotype was not possible. The distribution of the ABO blood groups was, however, consistent with previously reported distributions in the United Kingdom.36
Finally, some data were self-reported and incident cases of, for example, hypertension and diabetes mellitus may have been missed if they were diagnosed and treated in outpatient settings and not reported by the participant during one of the follow-up visits at the UK Biobank assessment center. However, any possible measurement errors or misclassifications are likely biased towards the null and would, therefore, underestimated the presented risks associated with the ABO blood groups.
Future Perspectives
The differences between individuals with blood groups A and B invite further studies on the pathophysiological mechanisms underlying the increased risk of thromboembolic diseases, as well as the associations with hyperlipidemia, atherosclerosis, myocardial infarction, and heart failure.
Conclusions
Our study identified connections between the ABO blood group system with healthy aging and disease development. The determination of ABO blood groups could serve in blood group individualized approaches towards health maintenance and prevention of diseases.
Acknowledgments
We thank the Centre for Information Technology of the University of Groningen for their support and for providing access to the Peregrine high-performance computing cluster. We thank N. Verweij; Ruben N. Eppinga, MD; Tom Hendriks, MD; Yordi J. van de Vegte, BSc; M. Yldau van der Ende, BSc; Yanick Hagemeijer, MSc; and Jan-Walter Benjamins, BEng (Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands), for their contributions to the extraction and processing of data in the UK Biobank. None of the contributors received compensation except for their employment at the University Medical Center Groningen. This research has been conducted using the UK Biobank Resource under Application Number 15031.
Footnote
Nonstandard Abbreviations Acronyms
- OR
- odds ratio
- PE
- pulmonary thromboembolism
- SNP
- single-nucleotide polymorphism
- VWF
- von Willebrand factor
Supplemental Material
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Received: 26 July 2019
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