A Mendelian randomization study to assess the genetic liability of gastroesophageal reflux disease for cardiovascular diseases and risk factors

Sun, Xingang; Chen, Lu; Zheng, Liangrong

doi:10.1093/hmg/ddac162

Cited by 20 publications

(14 citation statements)

References 55 publications

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“…This database includes 232,0781 single-nucleotide polymorphisms (SNPs), of which 80 are signi cantly related to GERD. According to previous studies, these SNPs can explain the 3.9% difference between the types of GERD [21]. A general F statistic greater than 10 has been reported to be robust.…”

Section: Methodsmentioning

confidence: 80%

Causal analysis of the association between gastroesophageal reflux disease and idiopathic pulmonary fibrosis

Chen

Gong²,

Liu

et al. 2023

Preprint

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Background: Recent observational studies have provided evidence of a close association between gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF). However, determining the causal relationship between these two conditions remains a challenge. In this study, we employed Mendelian randomization (MR), a genetic method using genome-wide association studies (GWAS), to investigate the causal relationship between GERD and IPF. Methods: In order to evaluate the causality of GERD in IPF, multiple MR methods were employed utilizing the GWAS databases of GERD from 473,524 individuals and of IPF from 451,025. Sensitivity analysis was performed to evaluate the robustness of MR results. Additionally, multi-variant Mendelian randomization (MVMR) was utilized to evaluate potential confounding factors. Results: We found a significant causal relationship between GERD and IPF (odds ratio [OR]: 1.002, 95% confidence interval [CI]: 1.001–1.003, P <0.001). This finding was also supported by the Weighted median analysis (OR: 1.002, 95% CI: 1.002–1.003, P =0.021). The sensitivity analysis did not reveal any significant deviation from the main results. Furthermore, MVMR analysis demonstrated that GERD significantly increased the risk of IPF, even after controlling for possible confounding factors (OR: 1.001, 95% CI: 1.001–1.003, P =0.04). Conclusions: The results of our study provide strong evidence of a causal relationship between GERD and IPF. Based on these findings, it is recommended that interventions be implemented for individuals with GERD to prevent the development of IPF.

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Section: Methodsmentioning

confidence: 80%

Causal analysis of the association between gastroesophageal reflux disease and idiopathic pulmonary fibrosis

Chen

Gong²,

Liu

et al. 2023

Preprint

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“…In addition, the causality of the associations between gastroesophageal reflux disease and several CVDs was strengthened in an MR study. 34 This study also identified positive associations of gastritis and duodenitis and irritable bowel syndrome with the risk of CVD, which were explored in few studies with conflicting findings. 15,35 Future studies are warranted to confirm these associations.…”

Section: Discussionmentioning

confidence: 86%

Risk of incident cardiovascular disease among patients with gastrointestinal disorder: prospective cohort study of 340,862 individuals

Chen

Sun

et al. 2023

Preprint

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Background and Aims The associations between gastrointestinal diseases (GIs) and cardiovascular disease (CVD) were unclear. We conducted a prospective cohort study to explore their associations. Methods This study included 340,862 individuals without baseline CVD from the UK Biobank cohort. Individuals with and without GIs were followed up until the ascertainment of incident CVDs, including coronary heart disease (CHD), cerebrovascular disease (CeVD), and peripheral artery disease (PAD). The diagnosis of diseases was confirmed with combination of the nationwide inpatient data, primary care data, and cancer registries. A multivariable Cox proportional hazard regression model was used to estimate the associations between GIs and the risk of incident CVD. Results During a median follow-up of 12.4 years, 28,787 incident CVD cases were diagnosed. Individuals with GIs had an elevated risk of CVD (hazard ratio 1.38; 95% confidence interval 1.35-1.42, P<0.001). Eleven out of fifteen GIs were associated with an increased risk of CVD after Bonferroni-correction, including cirrhosis, non-alcoholic fatty liver disease, gastritis and duodenitis, irritable bowel syndrome, gastroesophageal reflux disease, peptic ulcer, celiac disease, pancreatitis, diverticular disease, biliary disease, and appendicitis. The associations were stronger among women, individuals aged ≤ 60 years, and those with body mass index ≥ 25 kg/m2. Conclusions This large-scale prospective cohort study revealed the associations of GIs with an increased risk of incident CVD, in particular CHD and PAD. These findings support the reinforced secondary CVD prevention among patients with gastrointestinal disorders.

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“…Another interesting finding of our study in the stronger associations of certain gastrointestinal diseases with early-onset dementia compared to late-onset dementia. The possible reason for the differences may be that early-onset dementia is mainly caused by vascular comorbidities 34 that have a high prevalence rate among patients with hepatic, 35 intestinal, 36 and esophageal 37 dysfunction. These findings not only deepen the understanding in the etiological differences between early- and late-onset dementia but also may guide the secondary prevention for patients with different gastrointestinal conditions.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal Diseases, Genetic Risk, and Incident Dementia: A Prospective Cohort Study in 352,463 Middle-Aged Adults

Yuan

Dan

Zhang

et al. 2022

Preprint

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Importance Although gastrointestinal disease affects gut microbiota and their metabolites associated with dementia risk, the associations between gastrointestinal diseases and the risk of incident dementia are not established. Objective To examine the associations between 14 gastrointestinal diseases and incident dementia. Design, setting, and participants Cohort study. This cohort analysis included 352,463 participants free of baseline dementia. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2018 or 2021. Exposures Fourteen baseline gastrointestinal diseases were defined with data from inpatient, primary care, national cancer registries and self-reported data. Polygenic risk score (RPS) and apolipoprotein E (APOE) was constructed by individuals' genetic data. Main Outcomes and Measures: Primary outcome was incident all-cause dementia ascertained via a inpatient, primary care, and national death registries. Secondary outcomes were risk of common subtypes of dementia, including Alzheimer's disease and vascular dementia as well as early-onset (i.e., with the onset age < 65 years) and late-onset (≥ 65 years) dementia by diagnosis age. Results During a median follow-up of 12.4 years among 352,463 participants (mean [SD] age, 55.8 [8.1] years; 54.1% were women), 5648 incident dementia cases were diagnosed. Seven gastrointestinal diseases showed significant associations with an increased risk of dementia after controlling covariates and multiple testing. Compared to individuals without gastrointestinal diseases, the risk of dementia increased from 26% (95% confidence interval 13%-41%) for patients with intestinal diverticular disease to 121% (95% confidence interval 57%-211%) for patients with cirrhosis. The associations were different between certain gastrointestinal diseases and dementia by onset age. The associations appeared to be stronger for cirrhosis (P = 0.001), irritable bowel syndrome (P < 0.001), gastritis and duodenitis (P = 0.002), gastroesophageal reflux disease (P < 0.001), and peptic ulcer (P = 0.030) with early-onset dementia. There were no multiplicative interactions for PRS or APOE (P > 0.05). Conclusions and relevance This study found associations of several gastrointestinal diseases with an increased risk of incident dementia, especially early-onset dementia. Our findings imply the great importance of dementia prevention among patients with gastrointestinal diseases.

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A Mendelian randomization study to assess the genetic liability of gastroesophageal reflux disease for cardiovascular diseases and risk factors

Cited by 20 publications

References 55 publications

Causal analysis of the association between gastroesophageal reflux disease and idiopathic pulmonary fibrosis

Causal analysis of the association between gastroesophageal reflux disease and idiopathic pulmonary fibrosis

Risk of incident cardiovascular disease among patients with gastrointestinal disorder: prospective cohort study of 340,862 individuals

Gastrointestinal Diseases, Genetic Risk, and Incident Dementia: A Prospective Cohort Study in 352,463 Middle-Aged Adults

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