Dataset Information

Peripheral Inflammatory Factors and Acute Myocardial Infarction Risk: A Mendelian Randomization Study.

ABSTRACT:

Background

Previous observational studies have confirmed the relationship between inflammation and acute myocardial infarction (AMI), but genetic evidence is still lacking. The aim of this study was to explore the bidirectional association of multiple peripheral inflammatory factors with this disease at the genetic level.

Methods

Summary data for AMI and several peripheral inflammatory factors (such as interleukin-10 and interleukin-18) were collected from published genome-wide correlation studies. Based on the correlation, independence, and exclusivity assumptions, a total of 9 to 110 instrumental variables were selected from these summary data to predict the above traits. Two-sample Mendelian randomization methods, including inverse-variance weighted (IVW), were used to make causal inferences between exposures and outcomes. Sensitivity analyses including Cochran's Q, MR-Egger intercept, leave-one-out, forest plot, and MR-PRESSO were adopted to assess heterogeneity and horizontal pleiotropy.

Results

The IVW reported that elevated peripheral levels of interleukin-10 and interleukin-18 were nominally associated with a reduced risk of AMI (OR = 0.876, 95% CI = 0.788 ~ 0.974, P = 0.015; OR = 0.934, 95% CI = 0.875 ~ 0.997, P = 0.040). The IVW also reported that the risk of AMI nominally increased the peripheral level of interleukin-10 (OR = 1.062, 95% CI = 1.003 ~ 1.124, P = 0.040). No significant heterogeneity or horizontal pleiotropy were found by sensitivity analyses.

Conclusion

Both interleukin-10 and interleukin-18 were peripheral inflammatory factors genetically associated with AMI. In particular, combined with previous knowledge, interleukin-10 may have a protective effect on the onset, progression, and prognosis of the disease.

SUBMITTER: Chen Y

PROVIDER: S-EPMC10558024 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Peripheral Inflammatory Factors and Acute Myocardial Infarction Risk: A Mendelian Randomization Study.

Chen Yaxi Y Zeng Ling L

Global heart 20231006 1

<h4>Background</h4>Previous observational studies have confirmed the relationship between inflammation and acute myocardial infarction (AMI), but genetic evidence is still lacking. The aim of this study was to explore the bidirectional association of multiple peripheral inflammatory factors with this disease at the genetic level.<h4>Methods</h4>Summary data for AMI and several peripheral inflammatory factors (such as interleukin-10 and interleukin-18) were collected from published genome-wide co ...[more]

PMID: 37811136

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Project description:BackgroundUrolithiasis is a prevalent condition encountered in urology. Over the past decade, its global incidence has been on an upward trajectory; paired with a high recurrence rate, this presents considerable health and economic burdens. Although inflammatory factors are pivotal in the onset and progression of urolithiasis, their causal linkages remain elusive.MethodMendelian randomization (MR) is predicated upon genome-wide association studies (GWASs). It integrates bioinformatics analyses to reveal causal relationships between exposures and outcomes, rendering it an effective method with minimized bias. Drawing from a publicly accessible GWAS meta-analysis comprising 8,293 samples, we identified 41 genetic variations associated with inflammatory cytokines as instrumental variables. Outcome data on upper urinary tract stones, which included renal and ureteral stones (9,713 cases and 366,693 controls), and lower urinary tract stones, including bladder and urethral stones (1,398 cases and 366,693 controls), were derived from the FinnGen Consortium R9 dataset. By leveraging the bidirectional MR methodology, we aimed to decipher the causal interplay between inflammatory markers and urolithiasis.ResultsOur study comprehensively elucidated the association between genetic inflammatory markers and urolithiasis via bidirectional Mendelian randomization. Post-MR analysis of the 41 genetic inflammation markers revealed that elevated levels of circulating interleukin-2 (IL-2) (OR = 0.921, 95% CI = 0.848-0.999) suggest a reduced risk for renal stone disease, while heightened stem cell growth factor beta (SCGF-β) (OR = 1.150, 95% CI = 1.009-1.310) and diminished macrophage inflammatory protein 1 beta (MIP-1β) (OR = 0.863, 95% CI = 0.779-0.956) levels suggest an augmented risk for lower urinary tract stones. Furthermore, renal stone disease appeared to elevate IL-2 (β = 0.145, 95% CI = 0.013-0.276) and cutaneous T cell-attracting chemokine (CTACK) (β = 0.145, 95% CI = 0.013-0.276) levels in the bloodstream, whereas lower urinary tract stones were linked to a surge in interleukin-5 (IL-5) (β = 0.142, 95% CI = 0.057-0.226), interleukin-7 (IL-7) (β = 0.108, 95% CI = 0.024-0.192), interleukin-8 (IL-8) (β = 0.127, 95% CI = 0.044-0.210), growth regulated oncogene alpha (GRO-α) (β = 0.086, 95% CI = 0.004-0.169), monokine induced by interferon-gamma (MIG) (β = 0.099, 95% CI = 0.008-0.191) and macrophage inflammatory protein 1 alpha (MIP-1α) (β = 0.126, 95% CI = 0.044-0.208) levels.ConclusionThese discoveries intimate the instrumental role of IL-2 in the onset and progression of upper urinary tract stones. SCGF-β and MIP-1β influence the development of lower urinary tract stones. Urolithiasis also impacts the expression of cytokines such as IL-2, CTACK, IL-5, IL-7, IL-8, GRO-α, MIG, and MIP-1α. There is a pressing need for further investigation to ascertain whether these biomarkers can be harnessed to prevent or treat urolithiasis.

Dataset Information

Peripheral Inflammatory Factors and Acute Myocardial Infarction Risk: A Mendelian Randomization Study.

Background

Methods

Results

Conclusion

Publications

Peripheral Inflammatory Factors and Acute Myocardial Infarction Risk: A Mendelian Randomization Study.

Similar Datasets

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