scholarly journals Smoking is significantly associated with increased risk of COVID-19 and other respiratory infections

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Daniel B. Rosoff ◽  
Joyce Yoo ◽  
Falk W. Lohoff
Keyword(s):  
Substance Use ◽  
Observational Studies ◽  
Respiratory Diseases ◽  
Cardiometabolic Risk ◽  
Mendelian Randomization ◽  
Respiratory Infections ◽  
European Ancestry ◽  
Cardiometabolic Diseases ◽  
Increased Risk ◽  
Impact Risk

AbstractObservational studies suggest smoking, cannabis use, alcohol consumption, and substance use disorders (SUDs) may impact risk for respiratory infections, including coronavirus 2019 (COVID-2019). However, causal inference is challenging due to comorbid substance use. Using summary-level European ancestry data (>1.7 million participants), we performed single-variable and multivariable Mendelian randomization (MR) to evaluate relationships between substance use behaviors, COVID-19 and other respiratory infections. Genetic liability for smoking demonstrated the strongest associations with COVID-19 infection risk, including the risk for very severe respiratory confirmed COVID-19 (odds ratio (OR) = 2.69, 95% CI, 1.42, 5.10, P-value = 0.002), and COVID-19 infections requiring hospitalization (OR = 3.49, 95% CI, 2.23, 5.44, P-value = 3.74 × 10−8); these associations generally remained robust in models accounting for other substance use and cardiometabolic risk factors. Smoking was also strongly associated with increased risk of other respiratory infections, including asthma-related pneumonia/sepsis (OR = 3.64, 95% CI, 2.16, 6.11, P-value = 1.07 × 10−6), chronic lower respiratory diseases (OR = 2.29, 95% CI, 1.80, 2.91, P-value = 1.69 × 10−11), and bacterial pneumonia (OR = 2.14, 95% CI, 1.42, 3.24, P-value = 2.84 × 10−4). We provide strong genetic evidence showing smoking increases the risk for COVID-19 and other respiratory infections even after accounting for other substance use behaviors and cardiometabolic diseases, which suggests that prevention programs aimed at reducing smoking may be important for the COVID-19 pandemic and have substantial public health benefits.

scholarly journals Association between systemic lupus erythematosus and cancer: findings from cohort studies and Mendelian randomization analysis

2021 ◽  
Author(s):  
Dongqing Gu ◽  
Mingshuang Tang ◽  
Huijie Cui ◽  
Min Zhang ◽  
Yutong Wang ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Lupus Erythematosus ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
European Ancestry ◽  
Mendelian Randomization Analysis ◽  
Increased Risk ◽  
Randomization Analysis

Abstract Background Observational studies suggested that systemic lupus erythematosus (SLE) was associated with an increased risk of cancer, however, the causal effect remains unclear. We aim to determine the causality between SLE and cancer using a meta-analysis and Mendelian randomization (MR) approach. Methods A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI), and the potentially causal relationships identified by observational studies were further validated using two-sample Mendelian randomization. Results Through meta-analysis of 43 cohort studies involving 231,499 patients, we observed an increased overall cancer risk among SLE patients (RR = 1.62, 95% CI, 1.47–1.79). Site-specific analysis suggested that SLE patients were associated with an increased risk of 17 cancers. Mendelian randomization analysis indicated that genetically predisposed SLE was causally associated with an increased risk of lymphoma (odds ratio = 1.0004, 95% CI, 1.0001–1.0007, P = 0.0035), whereas a decreased risk of bladder cancer (odds ratio = 0.9996, 95% CI, 0.9994–0.9998, P = 0.00004) in European ancestry. However, no relationship was observed between genetically predisposed SLE and risk of colon, pancreatic, lung, cervical and Non-melanoma skin cancer in European ancestry, liver cancer and lung cancer in Asian ancestry. Conclusions Findings from meta-analysis and Mendelian randomization analysis suggested that SLE might be causally associated with an increased risk of lymphoma. However, inconsistent results were observed between SLE and risk of bladder cancer.

scholarly journals A genetically-informed study disentangling the relationships between tobacco smoking, cannabis use, alcohol consumption, substance use disorders and respiratory infections, including COVID-19

2021 ◽  
Author(s):  
Daniel B. Rosoff ◽  
Joyce Yoo ◽  
Falk W. Lohoff
Keyword(s):  
Substance Use ◽  
Alcohol Consumption ◽  
Substance Use Disorders ◽  
Genome Wide Association Study ◽  
Respiratory Infections ◽  
Study Data ◽  
Cannabis Use ◽  
European Ancestry ◽  
Future Research ◽  
Increased Risk

ABSTRACTBackgroundObservational studies suggest smoking, cannabis use, alcohol consumption, cannabis use, and substance use disorders (SUDs) may play a role in the susceptibility for respiratory infections and disease, including coronavirus 2019 (COVID-2019). However, causal inference is challenging due to comorbid substance use.MethodsUsing genome-wide association study data of European ancestry (data from >1.7 million individuals), we performed single-variable and multivariable Mendelian randomization to evaluate relationships between smoking, cannabis use, alcohol consumption, SUDs, and respiratory infections.ResultsGenetically predicted lifetime smoking was found to be associated with increased risk for hospitalized COVID-19 (odds ratio (OR)=4.039, 95% CI 2.335-6.985, P-value=5.93×10−7) and very severe hospitalized COVID-19 (OR=3.091, 95% CI, 1.883-5.092, P-value=8.40×10−6). Genetically predicted lifetime smoking was also associated with increased risk pneumoniae (OR=1.589, 95% CI, 1.214-2.078, P-value=7.33×10−4), lower respiratory infections (OR=2.303, 95% CI, 1.713-3.097, P-value=3.40×10−8), and several others. Genetically predicted cannabis use disorder (CUD) was associated with increased bronchitis risk (OR=1.078, 95% CI, 1.020-1.128, P-value=0.007).ConclusionsWe provide strong genetic evidence showing smoking increases the risk for respiratory infections and diseases even after accounting for other substance use and abuse. Additionally, we provide find CUD may increase the risk for bronchitis, which taken together, may guide future research SUDs and respiratory outcomes.

scholarly journals Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Chi Chen ◽  
Yi Chen ◽  
Pan Weng ◽  
Fangzhen Xia ◽  
Qin Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Vitamin D ◽  
Cardiometabolic Risk ◽  
Mendelian Randomization ◽  
Cardiometabolic Risk Factors ◽  
Metabolic Traits ◽  
Increased Risk ◽  
Vitamin D Levels ◽  
Genetically Determined

Abstract Background Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology. Methods Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria. Results Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels. Conclusions We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.

scholarly journals Mendelian randomization does not support serum calcium in prostate cancer risk

2018 ◽  
Author(s):  
James Yarmolinsky ◽  
Katie Berryman ◽  
Ryan Langdon ◽  
Carolina Bonilla ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Causal Inference ◽  
Serum Calcium ◽  
Observational Studies ◽  
Advanced Prostate Cancer ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
A Genome ◽  
Increased Risk

AbstractBackground: Observational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies.Objective: We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer.Design: A genetic instrument was constructed using 5 single nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (N ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls).Results: We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/dL increase in calcium: 0.83, 95% CI: 0.63-1.08; P=0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5 mg/dL increase in calcium: 0.98, 95% CI: 0.57-1.70; P=0.93).Conclusions: Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

scholarly journals Are psychiatric disorders risk factors for COVID-19 susceptibility and severity? a two-sample, bidirectional, univariable and multivariable Mendelian Randomization study

2020 ◽  
Author(s):  
Jurjen J. Luykx ◽  
Bochao D. Lin
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Neuropsychiatric Disorders ◽  
Sensitivity Analyses ◽  
Effect Estimate ◽  
Genome Wide Association Studies ◽  
Genetic Liability ◽  
Increased Risk

AbstractImportanceObservational studies have suggested bidirectional associations between psychiatric disorders and COVID-19 phenotypes, but results of such studies are inconsistent. Mendelian Randomization (MR) may overcome limitations of observational studies, e.g. unmeasured confounding and uncertainties about cause and effect.ObjectiveTo elucidate associations between neuropsychiatric disorders and COVID-19 susceptibility and severity.MethodIn November, 2020, we applied a two-sample, bidirectional, univariable and multivariable MR design to genetic data from genome-wide association studies (GWASs) of neuropsychiatric disorders and COVID-19 phenotypes (released on 20 Oct. 2020). Our study population consisted of almost 2 million participants with either a (neuro)psychiatric disorder or data on COVID-19 status. Outcomes and exposures were anxiety, anxiety-and-stress related disorders, major depressive disorder, schizophrenia, bipolar disorder, schizophrenia-bipolar disorder combined (BIP-SCZ), and Alzheimer’s dementia on the one hand; and self-reported, confirmed, hospitalized, and very severe COVID-19 on the other.ResultsIn single-variable MR analysis the most significant and only Bonferroni-corrected significant result was found for BIP-SCZ (a combined anxiety of bipolar disorder and schizophrenia as cases vs. controls): the effect estimate was consistent with increased risk of COVID-19 (OR = 1.17, 95% CI, 1.06-1.28; p = 0.0012). Nominally significant univariable results were in line with slightly elevated risks of COVID-19 for genetic liabilities to bipolar disorder and schizophrenia. No COVID-19 phenotype consistently increased risk of (neuro)psychiatric disorders. In multivariable MR, bipolar disorder was the only phenotype showing a Bonferroni-corrected significant effect on a COVID-19 phenotype, namely severe COVID-19 (OR = 1.293; 95% CI, 1.095-1.527; p = 0.003). All sensitivity analyses confirmed the results.ConclusionsGenetic liability to bipolar disorder slightly increases COVID-19 susceptibility and severity. The contribution of bipolar disorder to these COVID-19 phenotypes was smaller than the odds ratios estimated by observational studies. Strength of association and direction of effect for genetic liability to schizophrenia were similar, albeit less significant. We found no consistent evidence of reverse effects, i.e. of genetic liability to COVID-19 on psychiatric disorders.

scholarly journals Smoking and COVID-19: A two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Bing-Kun Zheng ◽  
Na Li
Keyword(s):  
Observational Studies ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Dose Effect ◽  
Genetic Studies ◽  
Host Genetics ◽  
Causal Risk Factor ◽  
Increased Risk ◽  
Summary Data ◽  
Randomization Method

AbstractEvidence from observational studies suggested that smokers are at increased risk of coronavirus disease 2019 (COVID-19). We aimed to assess the causal effect of smoking on risk for COVID-19 susceptibility and severity using two-sample Mendelian randomization method. Smoking-associated variants were selected as instrument variables from two largest genetic studies. The latest summary data of COVID-19 that shared on Jan 18, 2021 by the COVID-19 Host Genetics Initiative was used. The present Mendelian randomization study provided genetic evidence that smoking was a causal risk factor for COVID-19 susceptibility and severity. In addition, there may be a dose-effect relationship between smoking and COVID-19 severity.

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Hypertension ◽  
2022 ◽  
Author(s):  
Maddalena Ardissino ◽  
Eric A.W. Slob ◽  
Ophelia Millar ◽  
Rohin K. Reddy ◽  
Laura Lazzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Increased Risk

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

scholarly journals Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review

2020 ◽  
Vol 7 (1) ◽  
pp. e000756
Author(s):  
Roshni Patel ◽  
Sumrah A Naqvi ◽  
Chris Griffiths ◽  
Chloe I Bloom
Keyword(s):  
Adverse Effects ◽  
Observational Studies ◽  
Respiratory Infections ◽  
Bone Fractures ◽  
Risk Of Bias ◽  
Systemic Effects ◽  
Inhaled Corticosteroid ◽  
Mineral Density ◽  
Increased Risk ◽  
Ocular Disorders

BackgroundOral corticosteroid use increases the risk of systemic adverse effects including osteoporosis, bone fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if inhaled corticosteroid (ICS) use in asthma is also associated with increased risk of systemic effects.MethodsMEDLINE and Embase databases were searched to identify studies that were designed to investigate ICS-related systemic adverse effects in people with asthma. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia or mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and Risk of Bias In Non-randomised Studies of Interventions-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies reporting each outcome.ResultsThirteen studies met the inclusion criteria, 2 trials and 11 observational studies. Study numbers by outcome were: six BMD, six respiratory infections (four pneumonia, one tuberculosis (TB), one non-TB mycobacteria), one ocular disorder (cataracts) and no diabetes. BMD studies found conflicting results (three found loss of BMD and three found no loss), but were limited by study size, short follow-up and lack of generalisability. Studies addressing infection risk generally found positive associations but suffered from a lack of power, misclassification and selection bias. The one study which assessed ocular disorders found an increased risk of cataracts. Most studies were not able to fully adjust for known confounders, including oral corticosteroids.ConclusionThere is a paucity of studies assessing systemic adverse effects associated with ICS use in asthma. Those studies that have been carried out present conflicting findings and are limited by multiple biases and residual confounding. Further appropriately designed studies are needed to quantify the magnitude of the risk for ICS-related systemic effects in people with asthma.

A cautionary note on using Mendelian randomization to examine the Barker hypothesis and Developmental Origins of Health and Disease (DOHaD)

2020 ◽  
pp. 1-6
Author(s):  
Shannon D’Urso ◽  
Geng Wang ◽  
Liang-Dar Hwang ◽  
Gunn-Helen Moen ◽  
Nicole M. Warrington ◽  
...  
Keyword(s):  
Cardiometabolic Risk ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Developmental Origins ◽  
Phenotypic Data ◽  
Barker Hypothesis ◽  
Maternal Genotype ◽  
Increased Risk ◽  
Offspring Genotype ◽  
Health And Disease

Abstract Recent studies have used Mendelian randomization (MR) to investigate the observational association between low birth weight (BW) and increased risk of cardiometabolic outcomes, specifically cardiovascular disease, glycemic traits, and type 2 diabetes (T2D), and inform on the validity of the Barker hypothesis. We used simulations to assess the validity of these previous MR studies, and to determine whether a better formulated model can be used in this context. Genetic and phenotypic data were simulated under a model of no direct causal effect of offspring BW on cardiometabolic outcomes and no effect of maternal genotype on offspring cardiometabolic risk through intrauterine mechanisms; where the observational relationship between BW and cardiometabolic risk was driven entirely by horizontal genetic pleiotropy in the offspring (i.e. offspring genetic variants affecting both BW and cardiometabolic disease simultaneously rather than a mechanism consistent with the Barker hypothesis). We investigated the performance of four commonly used MR analysis methods (weighted allele score MR (WAS-MR), inverse variance weighted MR (IVW-MR), weighted median MR (WM-MR), and MR-Egger) and a new approach, which tests the association between maternal genotypes related to offspring BW and offspring cardiometabolic risk after conditioning on offspring genotype at the same loci. We caution against using traditional MR analyses, which do not take into account the relationship between maternal and offspring genotypes, to assess the validity of the Barker hypothesis, as results are biased in favor of a causal relationship. In contrast, we recommend the aforementioned conditional analysis framework utilizing maternal and offspring genotypes as a valid test of not only the Barker hypothesis, but also to investigate hypotheses relating to the Developmental Origins of Health and Disease more broadly.

scholarly journals Prevalence of Selected Cardiometabolic Risk Factors in The Global ART-Naïve HIV Infected Population: A Protocol for a Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Peter Vanes Ebasone ◽  
Nasheeta Peer ◽  
Anastase Dzudie ◽  
Andre Pascal Kengne
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Cardiometabolic Risk ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Cardiometabolic Risk Factors ◽  
Lipoprotein Cholesterol ◽  
People Living With Hiv ◽  
Cardiometabolic Diseases ◽  
Increased Risk

Abstract Background People living with HIV/AIDS (PLHIV) are at increased risk of cardiometabolic diseases attributable to the effects of the virus, antiretroviral therapy (ART) and traditional risk factors found in the general population. Most studies have focused on assessing the effect of ART on cardiometabolic disease in PLHIV with fewer studies assessing the cardiometabolic risk profile prior to any exposure to ART. Therefore, this protocol is for a systematic review and meta-analysis to estimate the global prevalence of selected cardiometabolic risk factors in ART-naïve PLHIV and their association with HIV specific factors. Methods We shall conduct a systematic search of published literature for observational studies on the prevalence of obesity, hypertension, diabetes and dyslipidaemia (high Low-Density Lipoprotein Cholesterol, high Total Cholesterol, high Triglyceride, low High-Density Lipoprotein Cholesterol) in ART-naïve PLHIV and their association with HIV specific characteristics. We will search PubMed-MEDLINE, CINAHL, SCOPUS, Academic Search Premier, Africa-Wide Information and Africa Journals Online databases to identify relevant studies published before March 2021. Two authors will independently screen, select studies, extract data and conduct risk of bias assessments. Disagreements between the two authors will be resolved by consensus or consulting a third reviewer. Data consistently reported across studies will be pooled using random-effects meta-analysis. Heterogeneity will be evaluated using Cochrane’s Q statistic and quantified using I2 statistics. The Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) 2015 guidelines are used for the reporting of this systematic review protocol. Discussion This review will help determine the burden of selected cardiometabolic diseases in ART-naïve HIV-infected populations and the contribution of HIV infection, independent of ART, to cardiometabolic diseases in PLHIV. It will provide new information that can help orientate future research and potentially guide healthcare policy making. This is part of a thesis that will be submitted to the Faculty of Health Sciences, University of Cape Town, for the award of a PhD in Medicine with protocol ethical clearance number (UCT HREC 350/2021). Registration PROSPERO: CRD42021226001

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