Causal Associations Between Tobacco, Alcohol Use and Risk of Infectious Diseases: A Mendelian Randomization Study

Zhu, Hao; Zhan, Xiaowei; Wang, Congjie; Deng, Yuying; Li, Xiaoping; Song, Linru; Zhao, Lingyan

doi:10.1007/s40121-023-00775-4

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…To examine if the potential genetic tools related to micronutrients were linked to other traits like blood metabolites (Wei et al, 2023), BMI (Wang et al, 2023), insomnia (Thorkildsen et al, 2023), and lifetime smoking (Zhu et al, 2023), we employed PhenoScanner V2. The website http//www.phenoscanner.medschl.cam.ac.uk/ was accessed on 1 November 2023.…”

Section: Mr Analysismentioning

confidence: 99%

“…Although sensitivity analyses did not uncover any indications of bias that would make the MR estimates unreliable, we proceeded to examine the second characteristic linked to the leading SNP for Zn by utilizing the PhenoScanner tool [blood metabolites (Wei et al, 2023), BMI (Wang et al, 2023), insomnia (Thorkildsen et al, 2023), and lifetime smoking (Zhu et al, 2023)]. However, no connections were observed between Zn-related instrumental variables and reported risk factors (Supplementary Table S11).…”

Section: Confounder and Multivariable Mr Analysesmentioning

confidence: 99%

“…In recent years, although some factors potentially influencing sepsis have been identified, such as blood metabolites (Wei et al, 2023), body mass index (BMI) (Wang et al, 2023), insomnia (Thorkildsen et al, 2023), lifetime smoking (Zhu et al, 2023), the role of trace elements in the pathogenesis of sepsis remains unclear. Simultaneously, understanding the dysregulation of trace element metabolism in the pathogenesis of sepsis is not comprehensive (Guo et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

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Circulating micronutrient levels and their association with sepsis susceptibility and severity: a Mendelian randomization study

Wei,

Liu,

Mei

et al. 2024

Front. Genet.

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Background: Sepsis, a global health challenge, necessitates a nuanced understanding of modifiable factors for effective prevention and intervention. The role of trace micronutrients in sepsis pathogenesis remains unclear, and their potential connection, especially with genetic influences, warrants exploration.Methods: We employed Mendelian randomization (MR) analyses to assess the causal relationship between genetically predicted blood levels of nine micronutrients (calcium, β-carotene, iron, magnesium, phosphorus, vitamin C, vitamin B6, vitamin D, and zinc) and sepsis susceptibility, severity, and subtypes. The instrumental variables for circulating micronutrients were derived from nine published genome-wide association studies (GWAS). In the primary MR analysis, we utilized summary statistics for sepsis from two independent databases (UK Biobank and FinnGen consortium), for initial and replication analyses. Subsequently, a meta-analysis was conducted to merge the results. In secondary MR analyses, we assessed the causal effects of micronutrients on five sepsis-related outcomes (severe sepsis, sepsis-related death within 28 days, severe sepsis-related death within 28 days, streptococcal septicaemia, and puerperal sepsis), incorporating multiple sensitivity analyses and multivariable MR to address potential heterogeneity and pleiotropy.Results: The study revealed a significant causal link between genetically forecasted zinc levels and reduced risk of severe sepsis-related death within 28 days (odds ratio [OR] = 0.450; 95% confidence interval [CI]: 0.263, 0.770; p = 3.58 × 10−3). Additionally, suggestive associations were found for iron (increased risk of sepsis), β-carotene (reduced risk of sepsis death) and vitamin C (decreased risk of puerperal sepsis). No significant connections were observed for other micronutrients.Conclusion: Our study highlighted that zinc may emerges as a potential protective factor against severe sepsis-related death within 28 days, providing theoretical support for supplementing zinc in high-risk critically ill sepsis patients. In the future, larger-scale data are needed to validate our findings.

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Section: Mr Analysismentioning

confidence: 99%

Section: Confounder and Multivariable Mr Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating micronutrient levels and their association with sepsis susceptibility and severity: a Mendelian randomization study

Wei,

Liu,

Mei

et al. 2024

Front. Genet.

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“…Body mass index (BMI) and smoking are significant confounding factors in the relationship between ADs and sepsis [29][30][31][32] . Therefore, in evaluating the independent causal effects of ADs on susceptibility and the short-term mortality risk from sepsis, we conducted a multivariable Mendelian randomization (MVMP) analysis to adjust for BMI and smoking.…”

Section: Mendelian Randomization Analysesmentioning

confidence: 99%

Unravelling the Link Between Primary Sclerosing Cholangitis and Sepsis: A Mendelian Randomization Study

Chen,

Wu,

et al. 2024

Preprint

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Background: autoimmune diseases (ADS) are associated with sepsis. This study aims to investigate the causalities between ADs and sepsis using Mendelian randomization (MR). Methods: we extracted single-nucleotide polymorphisms (SNPs) closely associated with 10 ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS), inflammatory bowel disease (IBD), celiac disease (CD), psoriasis (PsO), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and ulcerative colitis (UC) from the GWAS. Two-sample MR analysis was conducted using GWAS data from the UK Biobank to assess the association between the liability of each ad and sepsis and sepsis-related 28-day mortality. The inverse variance-weighted (IVW) method was used as the primary analysis. If sig-nificant causal relationships are found (considering multiple comparisons) in the univariate MR analysis, multivariate MR (MVMR) analysis is performed to adjust for body mass index (BMI) and smoking. A series of sensitivity analyses were conducted to validate the robustness of the results. Results: after adjusting for multiple testing, MR analysis revealed that PSC patients are responsible for increased susceptibility to sepsis using the IVW method (OR:1.033, 95%CI:1.007-1.060, PFDR = 0.020). Further sensitivity analyses validated the robustness of the above association. Even after adjusting for BMI and smoking, the MVMR-IVW still displayed a positive correlation（OR:1.043, 95%CI:1.022-1.064, P-value for IVW = 3.32E-05） between PSC patients and susceptibility to sepsis. However, no significant causal relationship was observed between SLE, RA, T1D, MS, IBD, CD, PsO, PBC, and UC with susceptibility to sepsis or short-term death risk. Conclusions: our MR analysis revealed a genetic susceptibility of PSC to sepsis. However, no causal relationship was observed between SLE, RA, T1D, MS, IBD, CD, PsO, PBC, and UC with suscep-tibility to sepsis or short-term death risk. Keywords: autoimmune diseases; sepsis; primary sclerosing cholangitis; Mendelian randomization

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“…Of these, 31 articles that fulfilled the inclusion criteria were included in the study. The categorization of the included studies by outcome revealed the following: 14 articles related to circulatory system diseases [15][16][17][18][19][20][21], 27 addressing digestive system diseases [22][23][24][25][26][27], 1 concerning mental and behavioral disorders [28], 6 focusing on nervous system diseases [29][30][31][32][33][34], 26 on neoplasms [22,[35][36][37][38][39], 11 on other diseases [33,[40][41][42][43][44][45]. Furthermore, we extended to conducting 151 novel MR analyses, comprising 76 on alcohol consumption and 75 on problematic alcohol use.…”

Section: Literature Search Study Selection and De Novo Mrmentioning

confidence: 99%

Alcohol Exposure and Disease Associations: A Mendelian Randomization and Meta-Analysis on Weekly Consumption and Problematic Drinking

Li,

Zhang,

Chen

et al. 2024

Nutrients

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Alcohol consumption significantly impacts disease burden and has been linked to various diseases in observational studies. However, comprehensive meta-analyses using Mendelian randomization (MR) to examine drinking patterns are limited. We aimed to evaluate the health risks of alcohol use by integrating findings from MR studies. A thorough search was conducted for MR studies focused on alcohol exposure. We utilized two sets of instrumental variables—alcohol consumption and problematic alcohol use—and summary statistics from the FinnGen consortium R9 release to perform de novo MR analyses. Our meta-analysis encompassed 64 published and 151 de novo MR analyses across 76 distinct primary outcomes. Results show that a genetic predisposition to alcohol consumption, independent of smoking, significantly correlates with a decreased risk of Parkinson’s disease, prostate hyperplasia, and rheumatoid arthritis. It was also associated with an increased risk of chronic pancreatitis, colorectal cancer, and head and neck cancers. Additionally, a genetic predisposition to problematic alcohol use is strongly associated with increased risks of alcoholic liver disease, cirrhosis, both acute and chronic pancreatitis, and pneumonia. Evidence from our MR study supports the notion that alcohol consumption and problematic alcohol use are causally associated with a range of diseases, predominantly by increasing the risk.

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Causal Associations Between Tobacco, Alcohol Use and Risk of Infectious Diseases: A Mendelian Randomization Study

Cited by 8 publications

References 26 publications

Circulating micronutrient levels and their association with sepsis susceptibility and severity: a Mendelian randomization study

Circulating micronutrient levels and their association with sepsis susceptibility and severity: a Mendelian randomization study

Unravelling the Link Between Primary Sclerosing Cholangitis and Sepsis: A Mendelian Randomization Study

Alcohol Exposure and Disease Associations: A Mendelian Randomization and Meta-Analysis on Weekly Consumption and Problematic Drinking

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