Nonalcoholic or metabolic-associated fatty liver disease and colorectal polyps: evidence from meta-analysis and two-sample Mendelian randomization
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ABSTRACT:
SUBMITTER: Zhai D
PROVIDER: S-EPMC11341362 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:The risk factors for nonalcoholic fatty liver disease (NAFLD) have not been clearly identified. We conducted a Mendelian randomization (MR) study to explore this. Independent genetic variants strongly associated with 5 lifestyle and 9 metabolic factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for NAFLD were obtained from a GWAS meta-analysis of 8434 cases and 770,180 non-cases (discovery dataset) and another GWAS meta-analysis of 1483 cases and 17,781 non-cases (replication dataset). Univariable and multivariable MR analyses were performed. There were associations with NAFLD for lifetime smoking index (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.31-1.93 per SD-increase), body mass index (BMI, OR 1.33, 95% CI 1.23-1.43 per SD-increase), waist circumference (OR 1.82; 95% CI 1.48-2.24 per SD-increase), type 2 diabetes (OR 1.21, 95% CI 1.15-1.27 per unit increase in log-transformed odds), systolic blood pressure (OR 1.17; 95% CI 1.07-1.26 per 10 mmHg increase), high-density lipoprotein cholesterol (OR 0.84, 95% CI 0.77-0.90 per SD-increase), and triglycerides (OR 1.23, 95% CI 1.15-1.33 per SD-increase). The associations for type 2 diabetes, systolic blood pressure, triglycerides, but not for high-density lipoprotein cholesterol remained strong after adjusting for genetically-predicted BMI. Genetic liability to type 2 diabetes mediated 51.4% (95% CI 13.4-89.3%) of the BMI-effects on NAFLD risk. There were suggestive inverse associations of genetically-predicted alcohol, coffee, and caffeine consumption, and vigorous physical activity with NAFLD risk. This study identified several lifestyle and metabolic factors that may be causally implicated in NAFLD.
| S-EPMC9329390 | biostudies-literature
Project description:PurposeEpidemiological studies support a protective role of habitual coffee and caffeine consumption against the risk of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the causal relationship between coffee intake and the risk of NAFLD.MethodsWe performed a two-sample Mendelian randomization (MR) analysis using SNPs associated with habitual coffee intake in a published genome-wide association study (GWAS) as genetic instruments and summary-level data from a published GWAS of NAFLD (1122 cases and 399,900 healthy controls) in the UK Biobank. The causal relationship was estimated with the inverse weighted method using a 4-SNP and 6-SNP instrument based on the single largest non-UK Biobank GWAS (n = 91,462) and meta-analysis (n = 121,524) of GWAS data on habitual coffee intake, respectively. To maximize power, we also used up to 77 SNPs associated with coffee intake at a liberal significance level (p ≤ 1e-4) as instruments.ResultsWe observed a non-significant trend towards a causal protective effect of coffee intake on NAFLD based upon either the 4-SNP (OR: 0.76; 95% CI 0.51, 1.14, p = 0.19) or 6-SNP genetic instruments (OR: 0.77; 95% CI 0.48, 1.25, p = 0.29). The result also remains non-significant when using the more liberal 77-SNP instrument.ConclusionOur findings do not support a causal relationship between coffee intake and NAFLD risk. However, despite the largest-to-date sample size, the power of this study may be limited by the non-specificity and moderate effect size of the genetic alleles on coffee intake.
| S-EPMC7910323 | biostudies-literature
Project description:BackgroundVitamin D deficiency is associated with nonalcoholic fatty liver disease (NAFLD) in many cross-sectional studies. However, the causality between them has not been established. We used bi-directional mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and NAFLD.Methods9182 participants were included from a survey in East China from 2014 to 2016. We calculated weighted genetic risk scores (GRS) for 25(OH)D concentration and NAFLD based on 25(OH)D-related and NAFLD-related single nucleotide polymorphisms. Presence of liver steatosis was assessed using ultrasound. Instrumental variable was used to measure the causal relationship between them.ResultsAn SD increase in the 25(OH)D GRS was significantly associated with 25(OH)D (β 1.29, 95%CI -1.54, -1.04, P<0.05) but not with NAFLD (OR 0.97, 95%CI 0.92, 1.01). An SD increase in NAFLD GRS was also strongly associated with NAFLD (OR 1.09, 95%CI 1.04, 1.15, P<0.05) but not with 25(OH)D (β -0.15, 95%CI -0.41, 0.10). Using an instrumental variable estimator, no associations were found for genetically instrumented 25(OH)D with NAFLD and for genetically instrumented NAFLD with 25(OH)D.ConclusionOur results support the conclusion that there is no causal association between vitamin D and NAFLD using a bi-directional MR approach in a Chinese population.
| S-EPMC5835542 | biostudies-literature
Project description: Not available
| S-EPMC11243184 | biostudies-literature
Project description:Background and aimsNonalcoholic fatty liver disease (NAFLD) is an escalating global health concern with significant implications for cancers. A better understanding of the causal relationship between NAFLD and extrahepatic cancers might help in clinical management of NAFLD and prevent its adverse outcomes.MethodsThis study encompassed two complementary approaches. First, the cross-sectional analysis was performed to examine the association between NAFLD and extrahepatic cancers, utilizing individual-level data from the National Health and Nutrition Examination Survey (2017-March 2020, 2021-2023 cycles). Logistic regression model was utilized to evaluate the association. Subsequently, Mendelian randomization (MR) analysis was conducted to explore the causal association between NAFLD and extrahepatic cancers. Summary-level data for genetically predicted NAFLD and extrahepatic cancers were derived from large-scale genome-wide association studies (GWAS), IEU Open GWAS project and the UK Biobank. The inverse variance weighting (IVW) method with a random-effect model was utilized as the main analysis.ResultsA total of 10,010 participants were included in the cross-sectional analysis. No association was observed between NAFLD and extrahepatic cancers after adjusting for potential confounders, with odd ratios (ORs) ranging from 0.872 to 2.171. IVW MR analysis showed genetic liability to genetically predicted cALT and imaging-and-biopsy confirmed NAFLD were not causally associated with extrahepatic cancers, with ORs ranging from 0.957 to 1.118 (all p > 0.050). Moreover, genetically predicted cALT and imaging-and-biopsy confirmed NAFLD were causally associated with liver & bile duct cancer (OR = 1.001, 95% CI = 1.000-1.001, p = 0.011; OR = 1.001, 95% CI = 1.000-1.001, p < 0.001), reinforcing a well-documented link between NAFLD and liver & bile duct cancer.ConclusionOur findings demonstrated that NAFLD was not causally associated with common extrahepatic cancers. Further research is required to validate these results from a mechanistic perspective.
| S-EPMC11892145 | biostudies-literature
Project description:Background: Since the association of homocysteine and clinical results of observational studies are controversial on non-alcoholic fatty liver related disease, we compute the two-sample Mendelian Randomization (MR) study. Objective: To evaluate whether the plasma level of homocysteine has an effect on the risk of Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Cirrhosis after its progress, we investigated the causal relationships between plasma homocysteine and the three non-alcoholic fatty liver related diseases mentioned above. Design and methods: Summary estimates were elicited from the inverse-variance weighted (IVW) method through 12 single nucleotide polymorphisms (SNPs) which related to the plasma homocysteine, the SNPs were obtained from a large genome-wide association studies (GWAS) of 44,147 European participants. And the summary statistics for the latest and largest GWAS datasets for NAFLD (307576 in total and 1,578 cases), NASH (309055 in total and 99 cases) and Cirrhosis (306145 in total and 826 cases) were collected from Ristey FinnGen website where the association of genetic variations with blood metabolite levels was conducted using comprehensive metabolite profiling. The study was performed through two-sample MR method. Results: The result indicated that the plasma homocysteine is not significantly associated with NAFLD, and its progression, NASH and Cirrhosis. Conclusion: The evidence in this study is quite deficient to support the causal association of the individual plasma homocysteine with NAFLD, NASH and Cirrhosis, the putative of associations is not exist.
| S-EPMC9763576 | biostudies-literature
Project description:Background and aimsBoth nonalcoholic fatty liver disease (NAFLD) and cholelithiasis are highly prevalent hepatobiliary diseases with risk of progression into severe outcomes. Considering the close relationship between liver and gallbladder in anatomy and physiology, a potential causal relationship between NAFLD and cholelithiasis has been speculated.MethodsMendelian randomization (MR) was employed using genome-wide association study (GWAS) summary statistics in Million Veteran Program (MVP) for NAFLD, and statistics in UK biobank for cholelithiasis.ResultsOur results demonstrate that NAFLD has a causal effect on cholelithiasis risk (OR, 1.003; 95%CI, 1.000-1.006; p = 0.03). We also performed the sensitivity analysis and heterogeneity test to ensure the accuracy of outcome and avoid the reverse causality.ConclusionNAFLD should be regarded as a potential pathogenic factor in pathogenesis study of cholelithiasis, and be considered in assessment and treatment of cholelithiasis.
| S-EPMC10948589 | biostudies-literature
Project description:BackgroundThere are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer.MethodsData from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes.ResultsNo association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample.ConclusionsGenetic predisposition to NAFLD is not associated with pancreatic cancer risk.ImpactGiven the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.
| S-EPMC10529823 | biostudies-literature
Project description:Introduction Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are both chronic multisystem diseases that cause tremendous health burdens worldwide. Previous epidemiological studies have found a bidirectional relationship between these two diseases; however, their causality remains largely unknown. We aim to examine the causal relationship between NAFLD and T2DM. Methods The observational analysis included 2,099 participants from the SPECT-China study and 502,414 participants from the UK Biobank. Logistic regression and Cox regression models were used to examine the bidirectional association between NAFLD and T2DM. Two-sample Mendelian randomization (MR) analyses were conducted to investigate the causal effects of the two diseases using summary statistics of genome-wide association studies from the UK Biobank for T2DM and the FinnGen study for NAFLD. Results During the follow-up, 129 T2DM cases and 263 NAFLD cases were observed in the SPECT-China study, and 30,274 T2DM cases and 4,896 NAFLD cases occurred in the UK Biobank cohort. Baseline NAFLD was associated with an increased risk of incident T2DM in both studies (SPECT-China: OR: 1.74 (95% confidence interval (CI): 1.12–2.70); UK Biobank: HR: 2.16 (95% CI: 1.82–2.56)), while baseline T2DM was associated with incident NAFLD in the UK Biobank study only (HR: 1.58). Bidirectional MR analysis showed that genetically determined NAFLD was significantly associated with an increased risk of T2DM (OR: 1.003 (95% CI: 1.002–1.004, p< 0.001)); however, there was no evidence of an association between genetically determined T2DM and NAFLD (OR: 28.1 (95% CI: 0.7–1,143.0)). Conclusions Our study suggested the causal effect of NAFLD on T2DM development. The lack of a causal association between T2DM and NAFLD warrants further verification.
| S-EPMC10200946 | biostudies-literature
Project description:IntroductionPrevious observational studies have demonstrated the relationship between leisure sedentary behavior, physical activity, and nonalcoholic liver disease (NAFLD). However, whether these associations are causal or confounding factors remains unclear.MethodsPooled genetic data from the UK Biobank and other large genome-wide association studies (GWAS) were used to extract instrumental variables representing sedentary television watching, computer use, driving, vigorous physical activity (VPA), and moderate-to-vigorous physical activity (MVPA). The two-sample Mendelian randomization (MR) method was used to explain the causal relationship between them and NAFLD. The inverse variance of the weighted method was used as the main analysis method, and MR-Egger, weighted median, MR-PRESSO, and other supplementary methods were also used. A sensitivity analysis was also performed. Simultaneously, the common risk factors for NAFLD were further analyzed for potential mediating associations.ResultsWe observed that sedentary television viewing (odds ratio (OR): 1.84; 95% confidence interval (CI): 1.09-3.10; p = 0.021) and genetically predicted VPA duration (OR: 0.0033; 95% CI: 0.000015-0.70; p = 0.036) were suggestively associated with the risk of NAFLD. Using a computer (OR: 1.51; 95% CI: 0.47-4.81; p = 0.484), driving (OR: 0.78; 95% CI: 0.05-11.94; p = 0.858), and MVPA time (OR: 0.168; 95% CI: 0.01-2.81; p = 0.214) were not significantly associated with NAFLD. The role of heterogeneity versus pleiotropy was limited in all the analyses.DiscussionThis study supports the association between sedentary television watching and an increased risk of NAFLD, along with vigorous physical activity as a possible protective factor for NAFLD.
| S-EPMC10289033 | biostudies-literature