Genetically predicted tobacco consumption and risk of intracranial aneurysm: a Mendelian randomization study

Zeng, Chudai; Huang, Zheng; Tao, Wengui; Yan, Langchao; Tang, Dong; Chen, Fenghua; Li, Shifu

doi:10.1007/s11356-022-23074-w

Cited by 8 publications

(4 citation statements)

References 53 publications

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“…[29] MR studies have previously established causality between smoking, AAA, and intracranial aneurysm. [10,30] Our current analysis posits a potential causal link with TAA, although meta-analytic data did not achieve statistical significance. The meta-analysis did not reveal a statistically significant association between the 2 factors.…”

Section: Discussionmentioning

confidence: 61%

The causal relationship between smoking and thoracic aortic aneurysm: Evidence from Mendelian randomization analysis

Zhou,

Wang

2024

Medicine

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The potential role of smoking as a risk factor for thoracic aortic aneurysm is still a subject of debate. Therefore, it is important to systematically investigate the causal relationship between smoking and thoracic aortic aneurysm using Mendelian randomization methods. Genetic data were obtained from genome-wide association studies using the inverse variance weighting method as the primary approach. A thorough sensitivity analysis was conducted to ensure the reliability of the findings. Instrumental variables were assessed using the F statistic, and meta-analysis was employed to assess the average genetic predictive effect between smoking and thoracic aortic aneurysm. Our Mendelian randomization study found a positive association between smoking and thoracic aortic aneurysm. The odds ratios (OR) in the inverse variance weighting method were OR = 1.23 (95% confidence interval [CI] = 1.00–1.51; P = .053) and OR = 2.07 (95% CI = 1.10–3.91; P = .024). Furthermore, meta-analyses consistently demonstrated a positive causal relationship between ferritin and myocardial infarction, although statistical significance was not observed. The analysis results did not indicate any horizontal pleiotropy. Despite the presence of heterogeneity, the Mendelian randomization analysis still yielded significant results. This study employed Mendelian randomization to establish a positive association between smoking levels and the risk of thoracic aortic aneurysm. The genetic evidence reveals a causal relationship between the two, offering new insights for future interventions targeting thoracic aortic aneurysms.

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Section: Discussionmentioning

confidence: 61%

The causal relationship between smoking and thoracic aortic aneurysm: Evidence from Mendelian randomization analysis

Zhou,

Wang

2024

Medicine

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“…This helps alleviate concerns related to potential confounding and the reversal of causation ( 8 ). In contemporary times, numerous MR studies on intracranial aneurysms have emerged, contributing valuable clinical evidence ( 9 , 10 ). This highlights that MR serves as a reliable research method capable of addressing diverse inquiries.…”

Section: Introductionmentioning

confidence: 99%

Early sexual activity lowers the incidence of intracranial aneurysm: a Mendelian randomization investigation

Wu,

Akram,

Kadeer

et al. 2024

Front. Neurol.

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ObjectiveInvestigate the potential correlation between the age of initial sexual contact, the lifetime accumulation of sexual partners, and the occurrence of intracranial aneurysm (IA) employing a two-sample Mendelian randomization approach.MethodsThis research aims to elucidate the causal relationship between intracranial aneurysm (IA) and sexual variables. Two distinct sexual variables, specifically the age had first sexual intercourse (n = 406,457) and the lifetime number of sexual partners (n = 378,882), were employed as representative parameters in a two-sample Mendelian randomization (MR) study. Outcome data from 23 cohorts, comprising 5,140 cases and 71,934 controls, were gathered through genome-wide association studies (GWAS). To bolster analytical rigor, five distinct methodologies were applied, encompassing MR-Egger technique, weighted median, inverse variance weighted, simple modeling, and weighted modeling.ResultsOur investigation unveiled a causal relationship between the age first had sexual intercourse and the occurrence of intracranial aneurysm (IA), employing the Inverse Variance Weighted (IVW) approach [Odds Ratio (OR): 0.609, p-value: 5.684E-04, 95% Confidence Interval (CI): 0.459–0.807]. This association was notably significant in the context of unruptured intracranial aneurysms (uIA) using the IVW approach (OR: 0.392, p-value: 6.414E-05, 95% CI: 0.248–0.621). Conversely, our findings did not reveal any discernible link between the lifetime number of sexual partners and the occurrence of IA (IA group: OR: 1.346, p-value: 0.415, 95% CI: 0.659–2.749; SAH group: OR: 1.042, p-value: 0.943, 95% CI: 0.338–3.209; uIA group: OR: 1.990, p-value: 0.273, 95% CI: 0.581–6.814).ConclusionThe two-sample Mendelian Randomization (MR) study presented herein provides evidence supporting a correlation between the age of initial engagement in sexual activity and the occurrence of intracranial aneurysm (IA), with a noteworthy emphasis on unruptured intracranial aneurysms (uIA). Nevertheless, our investigation failed to establish a definitive association between IA and the cumulative lifetime number of sexual partners.

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“…Genetic research on IA has been complemented with the MR technique, which has revealed a link between increased genetic predictions of sex hormone binding globulin (SHBG), bioavailable testosterone (BioT) [ 28 ], serum calcium (S-Ca), and 25-hydroxyvitamin D (S-25OHD)[ 29 ] levels and a higher vulnerability to aneurysmal subarachnoid hemorrhage (aSAH). Additionally, demographic and lifestyle factors such as gender[ 30 ], smoking, high-fat diets, hypertension [ 31 ] and tobacco and alcohol consumption [ 32 ] also appear to influence related traits and increase the risk of IA. Notably, increasing serum magnesium levels has been found to decrease the risk of IA and associated bleeding [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

DNA methylation regulator-mediated modification patterns and risk of intracranial aneurysm: a multi-omics and epigenome-wide association study integrating machine learning, Mendelian randomization, eQTL and mQTL data

Maimaiti,

Turhon,

Abulaiti

et al. 2023

J Transl Med

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Background Intracranial aneurysms (IAs) pose a significant and intricate challenge. Elucidating the interplay between DNA methylation and IA pathogenesis is paramount to identify potential biomarkers and therapeutic interventions. Methods We employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association studies (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). Our sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA. Results We identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition. Conclusion These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although our study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis. Graphical Abstract

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Genetically predicted tobacco consumption and risk of intracranial aneurysm: a Mendelian randomization study

Cited by 8 publications

References 53 publications

The causal relationship between smoking and thoracic aortic aneurysm: Evidence from Mendelian randomization analysis

The causal relationship between smoking and thoracic aortic aneurysm: Evidence from Mendelian randomization analysis

Early sexual activity lowers the incidence of intracranial aneurysm: a Mendelian randomization investigation

DNA methylation regulator-mediated modification patterns and risk of intracranial aneurysm: a multi-omics and epigenome-wide association study integrating machine learning, Mendelian randomization, eQTL and mQTL data

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