Genetically instrumented blood lead was not associated with CAD (odds ratio (OR) 1.01 per effect size of log transformed blood lead, 95% confidence interval (CI) 0.97, 1.05), blood pressure (systolic -0.18 mmHg, 95% CI -0.44 to 0.08 and diastolic -0.03 mmHg, 95% CI -0.09 to 0.15) or diabetes (OR 0.98, 95% CI 0.92 to 1.03) using MR-PRESSO estimates corrected for an outlier SNP (rs550057) from the highly pleiotropic gene ABO.
Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction = 0.10 in PanC4 and Pinteraction=0.13 in PanScan).
Our study demonstrates that pancreatic cancer risk is influenced by ABO status, in particular blood groups O and A<sub>1</sub> , and that this association may reflect also in tumor resectability and survival.
Interestingly, haplotype analysis indicated that the QAGA or H4 haplotype of ADAMTS13 gene had a protective effect on CAD after adjustment for ABO blood group [odds ratio (OR) = 0.3, 95% confidence interval (CI) = 0.1, 0.6] and major CAD risk factors (OR = 0.3, 95% CI = 0.1, 0.7).
The present study demonstrates that blood type O was independently and positively associated with an open culprit artery in patients with AMI, suggesting that the ABO blood type is not only associated with the susceptibility to coronary artery disease but also to spontaneous reperfusion in AMI patients.
Consistent with assessment using a false discovery rate approach, significant associations with ABO blood group were observed for cancer of the pancreas, breast, and upper gastrointestinal tract (mouth, salivary glands, pharynx, esophageal adenocarcinoma and stomach).
Genome-wide association studies (GWAS) identified several single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) and myocardial infarction (MI) locus in ABO gene.
Risk loci for ischemic stroke and its subtypes have been implicated in atrial fibrillation (PITX2 and ZFHX3), coronary artery disease (ABO, chr9p21, HDAC9, and ALDH2), blood pressure (ALDH2 and HDAC9), pericyte and smooth muscle cell development (FOXF2), coagulation (HABP2), carotid plaque formation (MMP12), and neuro-inflammation (TSPAN2).
Recently, one single nucleotide polymorphism (SNP) rs505922 in ABO gene has been implicated in susceptibility to pancreatic cancer across different populations, but different results were found in other types of cancer.
Our results are compatible with the previously reported association between the ABO gene and pancreatic cancer, and show that the effect of these common variants at the ABO locus on the P-LIP and ACE levels is largely opposing and pleiotropic.
Since glycosyltransferase activity, encoded by ABO, is higher for the A1 variant compared with the A2 variant, we investigated the hypothesis that A1 carriers were at an increased risk of pancreatic cancer.