Skip to content

Causal associations between serum bilirubin levels and decreased stroke risk: A two-sample Mendelian randomization study

Research output: Contribution to journalArticle

Standard

Causal associations between serum bilirubin levels and decreased stroke risk : A two-sample Mendelian randomization study. / Choi, Yoonjeong; Lee, Sun Ju; Spiller, Wes; Jung, Keum Ji; Lee, Ji-Young; Kimm, Heejin; Back, Joung Hwan; Lee, Sunmi; Jee, Sun Ha.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, 05.12.2019.

Research output: Contribution to journalArticle

Harvard

Choi, Y, Lee, SJ, Spiller, W, Jung, KJ, Lee, J-Y, Kimm, H, Back, JH, Lee, S & Jee, SH 2019, 'Causal associations between serum bilirubin levels and decreased stroke risk: A two-sample Mendelian randomization study', Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.119.313055.

APA

Choi, Y., Lee, S. J., Spiller, W., Jung, K. J., Lee, J-Y., Kimm, H., ... Jee, S. H. (2019). Causal associations between serum bilirubin levels and decreased stroke risk: A two-sample Mendelian randomization study. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.119.313055.

Vancouver

Author

Choi, Yoonjeong ; Lee, Sun Ju ; Spiller, Wes ; Jung, Keum Ji ; Lee, Ji-Young ; Kimm, Heejin ; Back, Joung Hwan ; Lee, Sunmi ; Jee, Sun Ha. / Causal associations between serum bilirubin levels and decreased stroke risk : A two-sample Mendelian randomization study. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2019.

Bibtex

@article{75ebcb4c510f4f1193840160207544bb,
title = "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 (MR) analyses conducted using a single sample have shown no evidence of association.Approach and Results: A two-sample summary MR study was performed by obtaining exposure and outcome data from separate non-overlapping samples. We utilised data from the Korean Genome and Epidemiology Study (KoGES) (n=25,406) and Korean Cancer Prevention Study-II (KCPS-II) (n=14,541) biobank for serum bilirubin and stroke respectively. Using KoGES, a total of 1,784 single nucleotide polymorphisms (SNPs) associated with serum bilirubin levels were discovered using a genome-wide significancethreshold (p < 5´10-8), of which 10 SNPs were identified as independent (R2 < 0.005) and adopted as genetic instruments. From KCPS-II, total and ischemic stroke cases were identified (n=1,489 and n=686), with 12,366 acting as controls. Various two-sample summary MR methods were employed, with MR estimates showing an inverse causal association between serum bilirubin levels and total stroke risk (Odds ratio=0.481, 95{\%} confidence interval=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{\%} confidence interval=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.",
keywords = "Bilirubin, Stroke, polymorphism, single nucleotide, genetic epidemiology, cardiovascular diseases, causality",
author = "Yoonjeong Choi and Lee, {Sun Ju} and Wes Spiller and Jung, {Keum Ji} and Ji-Young Lee and Heejin Kimm and Back, {Joung Hwan} and Sunmi Lee and Jee, {Sun Ha}",
year = "2019",
month = "12",
day = "5",
doi = "10.1161/ATVBAHA.119.313055.",
language = "English",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Causal associations between serum bilirubin levels and decreased stroke risk

T2 - A two-sample Mendelian randomization study

AU - Choi, Yoonjeong

AU - Lee, Sun Ju

AU - Spiller, Wes

AU - Jung, Keum Ji

AU - Lee, Ji-Young

AU - Kimm, Heejin

AU - Back, Joung Hwan

AU - Lee, Sunmi

AU - Jee, Sun Ha

PY - 2019/12/5

Y1 - 2019/12/5

N2 - Objective: A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization (MR) analyses conducted using a single sample have shown no evidence of association.Approach and Results: A two-sample summary MR study was performed by obtaining exposure and outcome data from separate non-overlapping samples. We utilised data from the Korean Genome and Epidemiology Study (KoGES) (n=25,406) and Korean Cancer Prevention Study-II (KCPS-II) (n=14,541) biobank for serum bilirubin and stroke respectively. Using KoGES, a total of 1,784 single nucleotide polymorphisms (SNPs) associated with serum bilirubin levels were discovered using a genome-wide significancethreshold (p < 5´10-8), of which 10 SNPs were identified as independent (R2 < 0.005) and adopted as genetic instruments. From KCPS-II, total and ischemic stroke cases were identified (n=1,489 and n=686), with 12,366 acting as controls. Various two-sample summary MR methods were employed, with MR estimates showing an inverse causal association between serum bilirubin levels and total stroke risk (Odds ratio=0.481, 95% confidence interval=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% confidence interval=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.

AB - Objective: A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization (MR) analyses conducted using a single sample have shown no evidence of association.Approach and Results: A two-sample summary MR study was performed by obtaining exposure and outcome data from separate non-overlapping samples. We utilised data from the Korean Genome and Epidemiology Study (KoGES) (n=25,406) and Korean Cancer Prevention Study-II (KCPS-II) (n=14,541) biobank for serum bilirubin and stroke respectively. Using KoGES, a total of 1,784 single nucleotide polymorphisms (SNPs) associated with serum bilirubin levels were discovered using a genome-wide significancethreshold (p < 5´10-8), of which 10 SNPs were identified as independent (R2 < 0.005) and adopted as genetic instruments. From KCPS-II, total and ischemic stroke cases were identified (n=1,489 and n=686), with 12,366 acting as controls. Various two-sample summary MR methods were employed, with MR estimates showing an inverse causal association between serum bilirubin levels and total stroke risk (Odds ratio=0.481, 95% confidence interval=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% confidence interval=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.

KW - Bilirubin

KW - Stroke

KW - polymorphism, single nucleotide

KW - genetic epidemiology

KW - cardiovascular diseases

KW - causality

U2 - 10.1161/ATVBAHA.119.313055.

DO - 10.1161/ATVBAHA.119.313055.

M3 - Article

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

ER -