Publication: Causal Associations of Urate With Cardiovascular Risk Factors: Two-Sample Mendelian Randomization
Issued Date
2021-07-08
Resource Type
ISSN
16648021
Other identifier(s)
2-s2.0-85111026191
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Frontiers in Genetics. Vol.12, (2021)
Suggested Citation
Thitiya Lukkunaprasit, Sasivimol Rattanasiri, Boonsong Ongphiphadhanakul, Gareth J. McKay, John Attia, Ammarin Thakkinstian Causal Associations of Urate With Cardiovascular Risk Factors: Two-Sample Mendelian Randomization. Frontiers in Genetics. Vol.12, (2021). doi:10.3389/fgene.2021.687279 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76105
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Causal Associations of Urate With Cardiovascular Risk Factors: Two-Sample Mendelian Randomization
Abstract
Background: Mendelian Randomization (MR) studies show conflicting causal associations of genetically predicted serum urate with cardiovascular risk factors (i.e., hypertension, diabetes, lipid profile, and kidney function). This study aimed to robustly investigate a causal relationship between urate and cardiovascular risk factors considering single nucleotide polymorphisms (SNPs) as instrumental variables using two-sample MR and various sensitivity analyses. Methods: Data on SNP-urate associations were taken from the Global Urate Genetics Consortium and data on SNP-cardiovascular risk factor associations were taken from various consortia/UK Biobank. SNPs were selected by statistically and biologically driven approaches as instrumental variables. Various sensitivity analyses were performed using different MR methods including inverse variance weighted, MR-Egger, weighted median/mode, MR-PRESSO, and the contamination mixture method. Results: The statistically driven approach showed significant causal effects of urate on HDL-C and triglycerides using four of the six MR methods, i.e., every 1 mg/dl increase in genetically predicted urate was associated with 0.047 to 0.103 SD decrease in HDL-C and 0.034 to 0.207 SD increase in triglycerides. The biologically driven approach to selection of SNPs from ABCG2, SLC2A9, SLC17A1, SLC22A11, and SLC22A12 showed consistent causal effects of urate on HDL-C from all methods with 0.038 to 0.057 SD decrease in HDL-C per 1 mg/dl increase of urate, and no evidence of horizontal pleiotropy was detected. Conclusion: Our study suggests a significant and robust causal effect of genetically predicted urate on HDL-C. This finding may explain a small proportion (7%) of the association between increased urate and cardiovascular disease but points to urate being a novel cardiac risk factor.