Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

Link: https://doi.org/10.1016/j.xkme.2022.100582
Authors: Dellepiane, Sergio; Paranjpe, Ishan; Rajagopal, Madhumitha; Kamat, Samir; O’Hagan, Ross; Gulamali, Faris; Rein, Joshua L; Charney, Alexander W; Do, Ron; Coca, Steven; Glicksberg, Benjamin S; Nadkarni, Girish N

Abstract: The association between cannabis use and chronic kidney disease (CKD) is controversial. We aimed to assess association of CKD with cannabis use in a large cohort study and then assess causality using Mendelian randomization with a genome-wide association study (GWAS). Retrospective cohort study and genome-wide association study. The retrospective study was conducted on the All of Us cohort (N=223,354). Genetic instruments for cannabis use disorder were identified from 3 GWAS: the Psychiatric Genomics Consortium Substance Use Disorders, iPSYCH, and deCODE (N=384,032). Association between genetic instruments and CKD was investigated in the CKDGen GWAS (N > 1.2 million). Cannabis consumption. CKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen. We conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization. Likely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry. Despite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.