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Bilirubin and Stroke Risk Using a Mendelian Randomization Design

Authors
 Sun Ju Lee  ;  Yon Ho Jee  ;  Keum Ji Jung  ;  Seri Hong  ;  Eun Soon Shin  ;  Sun Ha Jee 
Citation
 STROKE, Vol.48(5) : 1154-1160, 2017 
Journal Title
 STROKE 
ISSN
 0039-2499 
Issue Date
2017
MeSH
Adult ; Aged ; Bilirubin/blood* ; Bilirubin/genetics ; Cohort Studies ; Female ; Genome-Wide Association Study ; Glucuronosyltransferase/genetics* ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Republic of Korea ; Risk ; Stroke/blood* ; Stroke/genetics ; Tissue Banks*
Keywords
bilirubin ; causality ; epidemiology ; genes ; stroke
Abstract
BACKGROUND AND PURPOSE: Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. METHODS: The 14 single-nucleotide polymorphisms (SNPs) (<10-7) including rs6742078 of uridine diphosphoglucuronyl-transferase were selected from genome-wide association study of bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. RESULTS: Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. CONCLUSIONS: There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke.
Files in This Item:
T201702704.pdf Download
DOI
10.1161/STROKEAHA.116.015083
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jung, Keum Ji(정금지) ORCID logo https://orcid.org/0000-0003-4993-0666
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160584
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