Dataset Information

Causal Associations Between Serum Bilirubin Levels and Decreased Stroke Risk: A Two-Sample Mendelian Randomization Study.

ABSTRACT: OBJECTIVE:A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization analyses conducted using a single sample have shown no evidence of association. Approach and Results: A 2-sample summary Mendelian randomization study was performed by obtaining exposure and outcome data from separate nonoverlapping samples. We utilized data from the KoGES (Korean Genome and Epidemiology Study; n=25?406) and KCPS-II (Korean Cancer Prevention Study-II; n=14?541) biobank for serum bilirubin and stroke, respectively. Using KoGES, a total of 1784 single nucleotide polymorphisms associated with serum bilirubin levels were discovered using a genome-wide significance threshold (P<5×10-8), of which 10 single nucleotide polymorphisms were identified as independent (R2<0.005) and adopted as genetic instruments. From KCPS-II, total and ischemic stroke cases were identified (n=1489 and n=686), with 12?366 acting as controls. Various 2-sample summary Mendelian randomization methods were employed, with Mendelian randomization estimates showing an inverse causal association between serum bilirubin levels and total stroke risk (odds ratio, 0.481 [95% CI, 0.234-0.988]; P=0.046). This association increased in magnitude when restricting the analysis to ischemic stroke cases (odds ratio, 0.302 [95% CI, 0.105-0.868]; P=0.026). CONCLUSIONS:Our findings provide evidence of significant causal relationship between high levels of bilirubin and decreased stroke risk in Korean population in agreement with observational approaches. This highlights the potential for bilirubin to serve as a therapeutic target for oxidative stress-related diseases such as stroke and suggests that previous findings were not a consequence of unmeasured confounding.

SUBMITTER: Choi Y

PROVIDER: S-EPMC6975519 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Causal Associations Between Serum Bilirubin Levels and Decreased Stroke Risk: A Two-Sample Mendelian Randomization Study.

Choi Yoonjeong Y Lee Sun Ju SJ Spiller Wes W Jung Keum Ji KJ Lee Ji-Young JY Kimm Heejin H Back Joung Hwan JH Lee Sunmi S Jee Sun Ha SH

Arteriosclerosis, thrombosis, and vascular biology 20191205 2

<h4>Objective</h4>A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization analyses conducted using a single sample have shown no evidence of association. Approach and Results: A 2-sample summary Mendelian randomization study was performed by obtaining exposure and outcome data from separate nonoverlapping samples. We utilized data from the KoGES (Korean Genome ...[more]

PMID: 31801373

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.

Dataset Information

Causal Associations Between Serum Bilirubin Levels and Decreased Stroke Risk: A Two-Sample Mendelian Randomization Study.

Publications

Causal Associations Between Serum Bilirubin Levels and Decreased Stroke Risk: A Two-Sample Mendelian Randomization Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets