TY - JOUR
T1 - Cannabis Use and CKD
T2 - Epidemiological Associations and Mendelian Randomization
AU - Dellepiane, Sergio
AU - Paranjpe, Ishan
AU - Rajagopal, Madhumitha
AU - Kamat, Samir
AU - O'Hagan, Ross
AU - Gulamali, Faris
AU - Rein, Joshua L.
AU - Charney, Alexander W.
AU - Do, Ron
AU - Coca, Steven
AU - Glicksberg, Benjamin S.
AU - Nadkarni, Girish N.
N1 - Funding Information:
Dr Do is supported by the National Institute of General Medical Sciences of the NIH ( R35-GM124836 ) and the National Heart, Lung, and Blood Institute of the NIH ( R01-HL139865 and R01-HL155915 ). Dr Nadkarni also is supported by R01-DK127139 , R01-HL155915 , R56-DK126930 , and R01-DK118222 . ISF is supported by the National Institute of General Medical Sciences of the NIH ( T32-GM007280 ).
Funding Information:
Dr Do reported receiving grants from AstraZeneca ; grants and nonfinancial support from Goldfinch Bio ; being a scientific cofounder, consultant, and equity holder for Pensieve Health; and being a consultant for Variant Bio. Dr Nadkarni reports grants, personal fees, and nonfinancial support from Renalytix . Dr Nadkarni reports nonfinancial support from Pensieve Health , personal fees from AstraZeneca, personal fees from BioVie, personal fees from Siemens Healthineers, personal fees from Reata, and personal fees from GLG Consulting from outside the submitted work. The remaining authors declare that they have no relevant financial interests.
Publisher Copyright:
© 2022 The Authors
PY - 2023/2
Y1 - 2023/2
N2 - Rationale & Objective: 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). Study Design: Retrospective cohort study and genome-wide association study. Setting & Participants: 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). Exposure: Cannabis consumption. Outcomes: CKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen. Analytical Approach: We conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization. Results: In the retrospective study, compared to former users, less than monthly (OR, 1.01; 95% CI, 0.87-1.18; P = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52; P = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60; P = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50; P = 0.02) was significantly associated with CKD, adjusted for multiple confounders. In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD (OR, 1.00; 95% CI, 0.99-1.01; P = 0.96). These results were robust across different Mendelian randomization techniques and multiple kidney traits. Limitations: Likely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry. Conclusions: Despite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.
AB - Rationale & Objective: 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). Study Design: Retrospective cohort study and genome-wide association study. Setting & Participants: 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). Exposure: Cannabis consumption. Outcomes: CKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen. Analytical Approach: We conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization. Results: In the retrospective study, compared to former users, less than monthly (OR, 1.01; 95% CI, 0.87-1.18; P = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52; P = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60; P = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50; P = 0.02) was significantly associated with CKD, adjusted for multiple confounders. In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD (OR, 1.00; 95% CI, 0.99-1.01; P = 0.96). These results were robust across different Mendelian randomization techniques and multiple kidney traits. Limitations: Likely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry. Conclusions: Despite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.
KW - Cannabis
KW - Mendelian randomization
KW - chronic kidney disease
UR - http://www.scopus.com/inward/record.url?scp=85146556688&partnerID=8YFLogxK
U2 - 10.1016/j.xkme.2022.100582
DO - 10.1016/j.xkme.2022.100582
M3 - Article
AN - SCOPUS:85146556688
SN - 2590-0595
VL - 5
JO - Kidney Medicine
JF - Kidney Medicine
IS - 2
M1 - 100582
ER -