Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density: A Mendelian Randomization Study

Yuan, Shuai; Michaëlsson, Karl; Wan, Zhongmin; Larsson, Susanna C.

doi:10.1007/s00223-019-00606-0

Cited by 53 publications

(37 citation statements)

References 40 publications

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“…These analyses broaden the evidence base for the harmful effect of cigarette smoking, which has previously been demonstrated for most cardiovascular diseases [44,45], type 2 diabetes [46], and bone fracture [47]. Those findings along with results of the present study provide further evidential support for public health interventions to reduce cigarette smoking initiation in the population, and suggest that these strategies will have an important impact on lessening the burden of major diseases, and of cancer in particular.…”

Section: Discussionsupporting

confidence: 80%

Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants

et al. 2020

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Background Smoking is a well-established cause of lung cancer and there is strong evidence that smoking also increases the risk of several other cancers. Alcohol consumption has been inconsistently associated with cancer risk in observational studies. This mendelian randomisation (MR) study sought to investigate associations in support of a causal relationship between smoking and alcohol consumption and 19 site-specific cancers. Methods and findings We used summary-level data for genetic variants associated with smoking initiation (ever smoked regularly) and alcohol consumption, and the corresponding associations with lung, breast, ovarian, and prostate cancer from genome-wide association studies consortia, including participants of European ancestry. We additionally estimated genetic associations with 19 site-specific cancers among 367,643 individuals of European descent in UK Biobank who were 37 to 73 years of age when recruited from 2006 to 2010. Associations were considered statistically significant at a Bonferroni corrected p-value below 0.0013. Genetic predisposition to smoking initiation was associated with statistically significant higher odds of lung cancer in the International Lung Cancer Consortium (odds ratio [OR] 1.80; 95% confidence interval [

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Section: Discussionsupporting

confidence: 80%

Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants

et al. 2020

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“…Third, an observational study found a U-shaped association between LDL-C and COVID-19 severity [ 54 ]. However, as two-sample MR analysis based on summary-level data assumes a linear relationship between exposure and outcome, we could not test for a nonlinear relationship between LDL-C and COVID-19 severity [ 38 ]. Fourth, our MR analysis was based on populations of European ancestry, and the findings are unlikely to be generalized to other populations.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding MR to estimate the causal effect of TGs on COVID-19 severity, we added the following two analyses: we searched for SNVs associated with P < 5.0 × 10 –8 with pleiotropic effects on BMI and any type of leukocyte or inflammatory marker using the web tool PhenoScanner (version 2) [ 35 , 36 ] and then excluded them from the IVW method; we conducted the MR-PRESSO (Pleiotropy RESidual Sum and Outlier) global test with the run_mr_presso function to detect possible horizontal pleiotropy [ 37 ]. Moreover, we conducted IVW multivariable MR analyses with the mv_ivw function to estimate the direct effects of genetically predicted TG levels on risk of COVID-19 independent of the effects of other exposure traits using genetically predicted Apo-B, LDL-C, or BMI traits as a covariate [ 13 , 38 – 41 ].…”

Section: Methodsmentioning

confidence: 99%

Estimating causal effects of atherogenic lipid-related traits on COVID-19 susceptibility and severity using a two-sample Mendelian randomization approach

2021

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Background As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach. Methods We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls). We performed two-sample MR analyses using the inverse variance weighted (IVW) method. As sensitivity analyses, the MR-Egger regression, weighted median, and weighted mode methods were conducted as were leave-one-out sensitivity analysis, the MR-PRESSO global test, PhenoScanner searches, and IVW multivariable MR analyses. A P value below 0.0055 with Bonferroni correction was considered statistically significant. Results This MR study suggested that serum apolipoprotein B or LDL-cholesterol levels were not significantly associated with COVID-19 risk. On the other hand, we inferred that higher serum triglyceride levels were suggestively associated with higher risks of COVID-19 susceptibility (odds ratio [OR] per standard deviation increase in lifelong triglyceride levels, 1.065; 95% confidence interval [CI], 1.001–1.13; P = 0.045) and hospitalization (OR, 1.174; 95% CI, 1.04–1.33; P = 0.012), and were significantly associated with COVID-19 severity (OR, 1.274; 95% CI, 1.08–1.50; P = 0.004). Sensitivity and bidirectional MR analyses suggested that horizontal pleiotropy and reverse causation were unlikely. Conclusions Our MR study indicates a causal effect of higher serum triglyceride levels on a greater risk of COVID-19 severity in the European population using the latest and largest GWAS datasets to date. However, as the underlying mechanisms remain unclear and our study might be still biased due to possible horizontal pleiotropy, further studies are warranted to validate our findings and investigate underlying mechanisms.

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“…Patients with schizophrenia have an increased risk of diabetes mellitus, which is the key risk factor for fractures in the general population [44]. Furthermore, smoking and alcohol use disorder are common in patients with schizophrenia, both of which are established risk factors for osteoporosis and osteoporotic fracture [45,46]. Some studies have focused on the in uence of sex on fracture risk in patients with schizophrenia, and the results have been somewhat unclear.…”

Section: Discussionmentioning

confidence: 99%

Hip, Vertebral, and Wrist Fracture Risks and Schizophrenia: A Nationwide Longitudinal Study

Chu¹,

Chen²,

Yang³

et al. 2021

Preprint

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Background: Fractures are a great health issue associated with morbidity, quality of life, life span, and health care expenditure. Fractures are correlated with cardiovascular disease, type 2 diabetes mellitus, cerebrovascular disease, and some psychiatric disorders. However, representative national data are few, and longitudinal cohort studies on the association between schizophrenia and the subsequent fracture risk are scant. We designed a nationwide population-based cohort study to investigate the association of schizophrenia with hip, vertebral, and wrist fractures over a 10-year follow-up. Methods: Data of patients with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification code 295) and matched over January 2000–December 2009) were extracted from Taiwan National Health Insurance Research Database. A Cox proportional-hazards regression model was constructed to calculate hazard ratios (HRs) for fractures between the schizophrenia and control cohorts. Results: Of 2,028 people with schizophrenia (mean age: 36.3 years, 49.4% female), 89 (4.4%) reported newly diagnosed fractures—significantly higher than the proportion in the control population (257, 3.2%; P = 0.007). The incidences of hip (1.2%, P = 0.009) and vertebral (2.6%, P = 0.011) fractures were significantly higher in the schizophrenia cohort than in the control cohort. In Cox regression analysis, hip (adjusted HR: 1.78, 95% confidence interval [CI]: 1.08–2.93) and vertebral (adjusted HR: 1.40, 95% CI: 1.01–1.95) fracture risks were significantly higher in patients with schizophrenia. Furthermore, a sex-based subgroup analysis revealed that the risk of hip fracture remained significantly higher in female patients with schizophrenia (HR: 2.68, 95% CI: 1.32–5.44) than in female controls. On the other hand, there was no significant interaction between effects of sex and schizophrenia on the risk of fractures. Conclusions: Over a 10-year follow-up, hip and vertebral fracture risks were higher in the people with schizophrenia than in the controls. The risk of fractures in patients with schizophrenia does not differ between female and male.

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Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density: A Mendelian Randomization Study

Cited by 53 publications

References 40 publications

Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants

Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants

Estimating causal effects of atherogenic lipid-related traits on COVID-19 susceptibility and severity using a two-sample Mendelian randomization approach

Hip, Vertebral, and Wrist Fracture Risks and Schizophrenia: A Nationwide Longitudinal Study

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