Dataset Information

Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis.

ABSTRACT:

Background

People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer.

Methods

We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations between genetic liability to VTE and risk of 18 different cancers.

Results

We found no conclusive evidence that genetic liability to VTE was causally associated with an increased incidence of cancer, or vice versa. We observed an association between liability to VTE and pancreatic cancer risk [odds ratio for pancreatic cancer: 1.23 (95% confidence interval: 1.08-1.40) per log-odds increase in VTE risk, P = 0.002]. However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence to suggest a causal relationship.

Conclusions

These findings do not support the hypothesis that genetic liability to VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesize evidence for these mechanisms.

SUBMITTER: Cornish N

PROVIDER: S-EPMC10859161 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis.

Cornish Naomi N Haycock Philip P Brenner Hermann H Figueiredo Jane C JC Galesloot Tessel E TE Grant Robert C RC Johansson Mattias M Mariosa Daniela D McKay James J Pai Rish R Pellatt Andrew J AJ Samadder N Jewel NJ Shi Jianxin J Thibord Florian F Trégouët David-Alexandre DA Voegele Catherine C Thirlwell Chrissie C Mumford Andrew A Langdon Ryan R

International journal of epidemiology 20240201 1

<h4>Background</h4>People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer.<h4>Methods</h4>We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations bet ...[more]

PMID: 38124529

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Project description:BackgroundObservational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them remains uncertain. This study aimed to evaluate the potential bidirectional causal relationship between AD and psychiatric disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), anorexia nervosa (AN), Tourette syndrome (TS), schizophrenia, and anxiety.MethodsBidirectional two-sample Mendelian randomization (MR) was employed to elucidate the causality between AD and psychiatric disorders, using summary statistics from the most comprehensive genome-wide association studies conducted on AD (Ncases = 60,653, Ncontrols = 804,329). Psychiatric disorders were derived from the Psychiatric Genomics Consortium and were independent of AD data sources. The MR analysis entailed the implementation of multiple methods, including the inverse variance weighted method, MR-Egger regression method, weighted median method, simple mode method, and weighted mode method.ResultsBidirectional two-sample MR analysis uncovered significant causal associations between AD and severe psychiatric disorders. Specifically, liability to AD was associated with increased risk of ADHD (OR = 1.116; 95% CI: [1.009, 1.234]; P = 0.033) and ASD (OR = 1.131; 95% CI: [1.023, 1.251]; P = 0.016). Additionally, evidence suggested that liability to ADHD (OR = 1.112; 95% CI: [1.094, 1.130]; P = 9.20e-40), liability to AN (OR = 1.1; 95% CI: [1.068, 1.134]; P = 4.45e-10) and liability to BD (OR = 1.067; 95% CI: [1.009, 1.128]; P = 0.023) were associated with an increased risk of AD. Only the causal association between AD and ASD was independent of the reverse effect bias. These causal associations were robust and not affected by biases of heterogeneity and horizontal pleiotropy.ConclusionsOur study emphasizes the significant causal association between AD and an increased risk of ASD, and also identifying BD and AN as risk factors for AD.

Dataset Information

Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis.

Background

Methods

Results

Conclusions

Publications

Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis.

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