We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Identifying Potential Therapeutic Applications and Diagnostic Harms of Increased Bilirubin Concentrations: A Clinical and Genetic Approach.
- Authors
Zanussi, Jacy T.; Zhao, Juan; Dorn, Chad A.; Liu, Ge; Feng, QiPing; Wei, WeiQi; Mosley, Jonathan D.; Stein, C. Michael; Kawai, Vivian K.
- Abstract
Bilirubin has antioxidant and anti‐inflammatory properties in vitro and in animal studies and protects against inflammatory, cardiovascular, and other diseases in observational studies; therefore, bilirubin has potential as a therapeutic agent. However, observational studies could be confounded by many factors. We used a genetic (n = 61,281) and clinical (n = 234,670) approach to define the association between bilirubin and 19 conditions with a putative protective signal in observational studies. We also tested if individuals with genetically higher bilirubin levels underwent more diagnostic tests. We used a common variant in UGT1A1 (rs6742078) associated with an 26% increase in bilirubin levels in the genetic studies. Carriers of the variant had higher bilirubin levels (P = 2.2 × 10−16) but there was no significant association with any of the 19 conditions. In a phenome‐wide association study (pheWAS) to seek undiscovered genetic associations, the only significant finding was increased risk of "jaundice‐not of newborn." Carriers of the variant allele were more likely to undergo an abdominal ultrasound (odds ratio = 1.04, [1.00–1.08], P = 0.03). In contrast, clinically measured bilirubin levels were significantly associated with 15 of the 19 conditions (P < 0.003) and with 431 clinical diagnoses in the pheWAS (P < 1 × 10−5 adjusted for sex, age, and follow‐up). With additional adjustment for smoking and body mass index, 7 of 19 conditions and 260 pheWAS diagnoses remained significantly associated with bilirubin levels. In conclusion, bilirubin does not protect against inflammatory or other diseases using a genetic approach; the many putative beneficial associations reported clinically are likely due to confounding.
- Subjects
BILIRUBIN; BODY mass index
- Publication
Clinical Pharmacology & Therapeutics, 2022, Vol 111, Issue 2, p435
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1002/cpt.2441