The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual's blood group. Previous studies have primarily focused on identifying associations between ABO blood groups and diseases risk. Here, we sought to test for association between ABO genotypes (OO, OA, AA; OB, BB, and AB) and a large set of common inflammatory and cardiovascular diseases in UK Biobank as well as disease-related protein biomarkers in NSPHS. We first tested for association by conducting a likelihood ratio test, testing whether ABO contributed significantly to the risk for 24 diseases, and 438 plasma proteins. For phenotypes with FDR < 0.05, we tested for pair-wise differences between genetically determined ABO genotypes using logistic or linear regression. Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, identified associations for both type 1 and type 2 diabetes, and provide additional evidence of significant differences between heterozygous and homozygous allele carriers for pulmonary embolism, deep vein thrombosis, but also for von Willebrand factor levels. Furthermore, the results indicated an additive effect between genotypes, even between the two most common A subgroups, A1 and A2. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 23 have never been linked to the ABO locus before. These results show the need of incorporating ABO genotype information in the consultation and management of patients at risk, rather than classifying patients into blood groups.

中文翻译：

---

英国生物库中人类 ABO 基因型的特征及其与常见炎症和心血管疾病的关联

ABO基因包含编码不同抗原的三个主要等位基因；A、B 和 O，它们决定了一个人的血型。以前的研究主要集中在确定 ABO 血型与疾病风险之间的关联。在这里，我们试图测试ABO基因型（OO、OA、AA；OB、BB和AB）与英国生物库中的大量常见炎症和心血管疾病以及 NSPHS 中与疾病相关的蛋白质生物标志物之间的关联。我们首先通过进行似然比测试来测试关联，测试是否ABO显着增加了 24 种疾病和 438 种血浆蛋白的风险。对于 FDR < 0.05 的表型，我们使用逻辑回归或线性回归测试了遗传确定的ABO基因型之间的成对差异。我们的研究证实了先前关于ABO与心血管疾病之间存在强关联的发现，确定了 1 型和 2 型糖尿病的关联，并提供了额外的证据表明杂合子和纯合子等位基因携带者在肺栓塞、深静脉血栓形成以及von Willebrand 因子水平。此外，结果表明基因型之间存在累加效应，即使在两个最常见的 A 亚组A1和A2之间也是如此. 此外，我们发现ABO对 39 种血浆蛋白有显着贡献，其中 23 种以前从未与ABO基因座相关。这些结果表明需要将ABO基因型信息纳入高危患者的会诊和管理中，而不是将患者分为血型。