Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference
نویسندگان
چکیده
BACKGROUND Elevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate causal relationships between a gene product and physiological outcomes. In this report, we demonstrate its use in assessing direct causal relations between serum bilirubin levels and CVD risk factors, including obesity, cholesterol, measures of vascular function and blood pressure. METHODS Study subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels. RESULTS Serum bilirubin levels were inversely associated with levels of several cardiovascular disease risk factors, including body mass index (p=0.003), LDL (p=0.0005) and total cholesterol (p=0.0002). In contrast, UGT1A1*28 genotype, a known cause of elevated bilirubin levels, was not significantly associated with any of these traditional CVD risk factors. We did observe an association between genotype and brachial artery diameter (p=0.003) and cold pressor reactivity (p=0.01). CONCLUSIONS Our findings imply that the observed association of serum bilirubin levels with body mass index and cholesterol are likely due to confounding and suggest that previously established CVD benefits of increased bilirubin may in part be mediated by the early regulation of vascular structure and reactivity.
منابع مشابه
Author's response to reviews Title: Association between bilirubin and cardiovascular disease risk factors: Using Mendelian randomization to assess causal inference Authors:
متن کامل
Bilirubin and Stroke Risk Using a Mendelian Randomization Design.
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 uridin...
متن کاملCirculating Total Bilirubin and Future Risk of Hypertension in the General Population: The Prevention of Renal and Vascular End‐Stage Disease (PREVEND) Prospective Study and a Mendelian Randomization Approach
BACKGROUND Circulating total bilirubin is known to be inversely and independently associated with future risk of cardiovascular disease. However, the relationship of circulating total bilirubin with incident hypertension is uncertain. We aimed to assess the association of total bilirubin with future hypertension risk and supplemented this with a Mendelian randomization approach to investigate a...
متن کاملNetwork Mendelian Randomization Study Design to Assess Factors Mediating the Causal Link Between Telomere Length and Heart Disease.
Mendelian randomization study designs represent new powerful tools available to researchers that enable causal inferences to be made about the effects of risk factors in health and disease outcomes in the context of a prospective observational study. These study designs involve estimating the association between a genetically modifiable risk factor and health and disease outcomes. If individual...
متن کاملMendelian randomization provides no evidence for a causal role of serum urate in increasing serum triglyceride levels.
BACKGROUND Triglycerides and their lipoprotein transport molecules are risk factors for heart disease. Observational studies have associated elevated levels of serum urate (SU) with triglycerides and risk of heart disease. However, owing to unmeasured confounding, observational studies do not provide insight into the causal relationship between SU and triglyceride. The aim of this study was to ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 12 شماره
صفحات -
تاریخ انتشار 2012