Objective: Observational studies demonstrate an inverse association between type II diabetes and abdominal aortic aneurysm (AAA) for reasons that are unclear. The aim of this study was to clarify the causal association between type II diabetes predisposition and AAA using Mendelian randomisation.
Methods: Effect estimates for single nucleotide polymorphisms (SNPs) associated with diabetes were obtained from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) consortium to construct a genetic instrumental variable. Corresponding effect estimates for associations of these SNPs with AAA were obtained from the International Aneurysm Consortium comprising six separate AAA genomewide association studies (4 972 cases and 99 858 controls). Mendelian randomisation estimates were calculated using inverse variance, weighted median, and MR-Egger methods, and compared against recently published observational estimates.
Results: A genetic risk score was constructed from 206 SNPs associated with diabetes. All three Mendelian randomisation models showed no effect of genetic liability to diabetes and risk of AAA (inverse variance: odds ratio 1.04 per unit higher log odds, 95% 0.98 - 1.11, p = .19; MR-Egger slope p = .33; weighted median p = .50). Results were similar after excluding the TCF7L2 locus (inverse variance p = .075). Findings from the Mendelian randomisation analysis differed from previous observational reports of an inverse association (p < .001).
Conclusion: Lifelong genetic predisposition to diabetes does not appear to protect against AAA. These findings differ from traditional epidemiological studies showing an inverse association between diabetes and AAA, for reasons that remain unclear.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejvs.2021.10.038 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Relationship Between Body Mass Index and Peripheral Artery Disease: Insights from the National Health and Nutrition Examination Survey and Mendelian Randomization Analysis.
J Surg Res
January 2025
School of Medicine, Tongji University, Shanghai, China; Department of Health Statistics, Navy Medical University, Shanghai, China. Electronic address:
Introduction: Body mass index (BMI) has been implicated in various cardiovascular conditions, but its association with peripheral artery disease (PAD) in both real-world and genetic studies have been contentious and debated.
Methods: This study enrolled 6707 individuals from the National Health and Nutrition Examination Survey database to investigate the association between BMI and the risk of PAD. The weighted logistic regression, restricted cubic spline, and subgroup analysis were performed using real-world data.
Associations between 25-hydroxyvitamin D/calcium/alkaline phosphatase levels and the risk of developing kidney stones: Results from NHANES (2013-2018)-based and Mendelian randomization studies.
Medicine (Baltimore)
January 2025
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
This study explores the relationship between 25-hydroxyvitamin D/calcium/alkaline phosphatase (ALP) levels and kidney stone development via cross-sectional and Mendelian randomization (MR) analyses. We used data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 to explore the associations of 25(OH)D metabolite, calcium, and ALP levels with kidney stone development, LDSC analysis to determine the associations between their genetically predicted levels and kidney stone development, and MR analysis to determine the causality of those relationship via genome-wide association studies (GWASs). The cross-sectional study revealed a relationship between ALP levels and kidney stone development (Model 1: OR = 1.
View Article and Find Full Text PDFThe role of inflammatory factors in mediating the causal effects of type 1 diabetes mellitus on idiopathic pulmonary fibrosis: A two-step Mendelian randomization study.
Medicine (Baltimore)
January 2025
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
While recent studies suggested a potential causal link between type 1 diabetes mellitus (T1DM) but not type 2 diabetes mellitus (T2DM) and idiopathic pulmonary fibrosis (IPF), the involved mechanism remains unclear. Here, using a Mendelian randomization (MR) approach, we verified the causal relationship between the two types of diabetes mellitus and IPF and investigated the possible role of inflammation in the association between diabetes mellitus and IPF. Based on genome-wide association study (GWAS) summary data of T1DM, T2DM, and IPF, the univariable MR, multivariable MR (MVMR), and mediation MR were successively used to analyze the causal relationship.
View Article and Find Full Text PDFCirculating inflammatory cytokines and colorectal cancer: New insights from Mendelian randomization.
Medicine (Baltimore)
January 2025
Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People's Republic of China.
Colorectal cancer (CRC) is one of the most common cancers worldwide and inflammation is believed to play an important role in CRC. In this study, we comprehensively analyzed the causal association between 91 circulating inflammatory cytokines and the risk of CRC using Mendelian randomization (MR). Based on genome-wide association study summary statistics, we examined the causal effects of 91 circulating inflammatory cytokines on CRC.
View Article and Find Full Text PDFAssociations of cathepsins with pulmonary arterial hypertension mediated by circulating metabolites: A Mendelian randomization study.
Medicine (Baltimore)
January 2025
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
The correlation between cathepsins and pulmonary arterial hypertension (PAH) is well-established, but the causative link between them remains uncertain. This study aimed to explore the causal role of circulating metabolites mediating cathepsins in PAH using Mendelian randomization (MR). A 2-sample 2-step MR method was used to identify causal relationship between cathepsins and PAH; causal relationship between circulating metabolites and PAH; and mediated effects of these circulating metabolites.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!