Dataset Information

Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.

ABSTRACT:

Background

Nonalcoholic fatty liver disease (NAFLD) has been linked to gallstone disease (GSD) in observational studies; however, the relationships between certain lipid profiles and GSD remain unclear.

Methods

We adopted a two-sample Mendelian randomization (MR) framework by applying different statistical methods to assess causalities between lipid profiles and GSD. We identified single-nucleotide polymorphisms (SNPs) for blood lipids and NAFLD from separate previous genome-wide association studies (GWASs).

Results

We retrieved GSD SNPs attributed to 10,520 cases and 361,194 controls and validated our estimates using GWAS summary data from UK Biobank. We also performed sex-stratified analyses. Based on the summary estimates of 41, 59, 35, and 2 SNPs for low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), triglycerides (TGs), and NAFLD, respectively, we found no evidence of a causal relationship between genetically-predicted lipid profiles and GSD. The odds ratios were 0.995 for LDLC [95% confidence interval (CI): 0.994-0.998] per 0.98 mmol/L, 0.999 for HDLC (95% CI: 0.996-1.003) per 0.41 mmol/L, 0.997 for TGs (95% CI: 0.994-1.001) per 1 mmol/L, and 0.993 for NAFLD (95% CI: 0.984-1.003). No evidence of associations between lipid profile s and GSD in validation MR analyses or the sex-stratification analyses was noted.

Conclusions

Genetically predicted hyperlipidemia or NAFLD is not causally associated with GSD.

SUBMITTER: Yuan X

PROVIDER: S-EPMC9403919 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.

Yuan Xiaofeng X Chen Haitian H Zeng Kaining K Xiao Jiaqi J Liu Jiaqing J Lin Guowang G Zhang Jiebin J Lu Tongyu T Cai Jianye J Yao Jia J Zhang Yingcai Y Sui Xin X Liang Jinliang J Zheng Jun J

Annals of translational medicine 20220801 15

<h4>Background</h4>Nonalcoholic fatty liver disease (NAFLD) has been linked to gallstone disease (GSD) in observational studies; however, the relationships between certain lipid profiles and GSD remain unclear.<h4>Methods</h4>We adopted a two-sample Mendelian randomization (MR) framework by applying different statistical methods to assess causalities between lipid profiles and GSD. We identified single-nucleotide polymorphisms (SNPs) for blood lipids and NAFLD from separate previous genome-wide ...[more]

PMID: 36035003

Similar Datasets

Project description:BackgroundAchilles tendinopathy (AT) is associated with severe pain and is the cause of dysfunction and disability that are associated with significant reduction in social and economic benefits. Several potential risk factors have been proposed to be responsible for AT development; however, the results of observational epidemiological studies remain controversial, presumably because the designs of these studies are subject to residual confounding and reverse causality. Mendelian randomization (MR) can infer the causality between exposure and disease outcomes using genetic variants as instrumental variables, and identification of the causal risk factors for AT is beneficial for early intervention. Thus, we employed the MR strategy to evaluate the causal associations between previously reported risk factors (anthropometric parameters, lifestyle factors, blood biomarkers, and systemic diseases) and the risk of AT.MethodsUnivariable MR was performed to screen for potential causal associations between the putative risk factors and AT. Bidirectional MR was used to infer reverse causality. Multivariable MR was conducted to investigate the body mass index (BMI)-independent causal effect of other obesity-related traits, such as the waist-hip ratio, on AT.ResultsUnivariable MR analyses with the inverse-variance weighted method indicated that the genetically predicted BMI was significantly associated with the risk of AT (P=2.0×10-3), and the odds ratios (95% confidence intervals) is 1.44 (1.14-1.81) per 1-SD increase in BMI. For the other tested risk factors, no causality with AT was identified using any of the MR methods. Bidirectional MR suggested that AT was not causally associated with BMI, and multivariable MR indicated that other anthropometric parameters included in this study were not likely to causally associate with the risk of AT after adjusting for BMI.ConclusionsThe causal association between BMI and AT risk suggests that weight control is a promising strategy for preventing AT and alleviating the corresponding disease burden.

Project description:BackgroundSeveral observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers.MethodsWe conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers.ResultsAfter correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10-5) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10-5). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997-1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992-1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS.ConclusionsSS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies.

Dataset Information

Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.

Background

Methods

Results

Conclusions

Publications

Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets