Dataset Information

Serum bilirubin and kidney function: a Mendelian randomization study.

ABSTRACT:

Background

Further investigation is needed to determine the causal effects of serum bilirubin on the risk of chronic kidney disease (CKD).

Methods

This study is a Mendelian randomization (MR) analysis. Among the well-known single-nucleotide polymorphisms (SNPs) related to serum bilirubin levels, rs4149056 in the SLCO1B1 gene was selected as the genetic instrument for single-variant MR analysis, as it was found to be less related to possible confounders than other SNPs. The association between genetic predisposition for bilirubin levels and estimated glomerular filtration rate (eGFR) or CKD was assessed in 337 129 individuals of white British ancestry from the UK Biobank cohort. Two-sample MR based on summary-level data was also performed. SNPs related to total or direct bilirubin levels were collected from a previous genome-wide association study and confounder-associated SNPs were discarded. The independent CKDGen meta-analysis data for CKD were employed as the outcome summary statistics.

Results

The alleles of rs4149056 associated with higher bilirubin levels were associated with better kidney function in the UK Biobank data. In the summary-level MR, both of the genetically predicted total bilirubin {per 5 µmol/L increase; odds ratio [OR] 0.931 [95% confidence interval (CI) 0.871-0.995]} and direct bilirubin [per 1 µmol/L increase; OR 0.910 (95% CI 0.834-0.993)] levels were significantly associated with a lower risk of CKD, supported by the causal estimates from various MR sensitivity analyses.

Conclusion

Genetic predisposition for higher serum bilirubin levels is associated with better kidney function. This result suggests that higher serum bilirubin levels may have causal protective effects against kidney function impairment.

SUBMITTER: Park S

PROVIDER: S-EPMC9394720 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Serum bilirubin and kidney function: a Mendelian randomization study.

Park Sehoon S Lee Soojin S Kim Yaerim Y Lee Yeonhee Y Kang Min Woo MW Kim Kwangsoo K Kim Yong Chul YC Han Seung Seok SS Lee Hajeong H Lee Jung Pyo JP Joo Kwon Wook KW Lim Chun Soo CS Kim Yon Su YS Kim Dong Ki DK

Clinical kidney journal 20220502 9

<h4>Background</h4>Further investigation is needed to determine the causal effects of serum bilirubin on the risk of chronic kidney disease (CKD).<h4>Methods</h4>This study is a Mendelian randomization (MR) analysis. Among the well-known single-nucleotide polymorphisms (SNPs) related to serum bilirubin levels, rs4149056 in the <i>SLCO1B1</i> gene was selected as the genetic instrument for single-variant MR analysis, as it was found to be less related to possible confounders than other SNPs. The ...[more]

PMID: 36003670

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Project description:BackgroundMany observational epidemiology studies discovered that kidney cancer and impaired kidney function have a bidirectional relationship. However, it remains unclear whether these two kinds of traits are causally linked. In this study, we aimed to investigate the bidirectional causal relation between kidney cancer and kidney function biomarkers (creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), serum urate, and urinary albumin-to-creatinine ratio (UACR)).MethodsFor both directions, single-nucleotide polymorphisms (SNPs), as genetic instruments, for the five kidney function traits were selected from up to 1,004,040 individuals, and SNPs for kidney cancer were from 408,786 participants(1338 cases). In the main analysis, we applied two state-of-the-art MR methods, namely, contamination mixture and Robust Adjusted Profile Score to downweight the effect of weak instrument bias, pleiotropy, and extreme outliers. We additionally conducted traditional MR analyses as sensitivity analyses. Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Kaiser Permanente.ResultsBased on 99 SNPs, we found that the eGFRcrea had a significant negative causal effect on the risk of kidney cancer (OR = 0.007, 95% CI:2.6 × 10-4 -0.569, p = 0.041). After adjusting for body composition or diabetes, urate had a significant negative causal effect on kidney cancer (OR <1, p < 0.05). For UACR, it showed a strong causal effect on kidney cancer, after adjusting for body composition (OR = 14.503, 95% CI: 2.546-96.001, p = 0.032). Due to lacking significant signals and effect power for the reverse MR, further investigations are warranted.ConclusionsOur study suggested a potential causal effect of damaged kidney function on kidney cancer. EGFRcrea and UACR might be causally associated with kidney cancer, especially when patients were comorbid with obesity or diabetes. We called for larger sample-size studies to further unravel the underlying causal relationship and the exact mechanism.

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Dataset Information

Serum bilirubin and kidney function: a Mendelian randomization study.

Background

Methods

Results

Conclusion

Publications

Serum bilirubin and kidney function: a Mendelian randomization study.

Similar Datasets

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