Stroke. 2017;48:1154-1160

 

Bilirubin and Stroke Risk Using a Mendelian

Randomization Design

Sun Ju Lee, Yon Ho Jee, Keum Ji Jung, Seri Hong, Eun Soon Shin, Sun Ha Jee

 

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.



Keyword : bilirubin causality epidemiology genes stroke