Cannabis use and obesity-traits: A Mendelian randomization study.

ABSTRACT

BACKGROUND: Observational studies suggested that cannabis use is associated with decreased body fatness; however, observational studies are subject to confounding, making causal inference and determining the direction of these associations difficult. We performed Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) to investigate the potential causal association of cannabis use and obesity-related traits. METHODS: We used 51 single nucleotide polymorphisms (SNPs) associated with lifetime cannabis use at P 1<× 10-5 from a GWAS of 184,765 individuals of European descent and 27 SNPs genome-wide associated with cannabis use disorder as instrumental variables. The GWAS for body mass index (BMI) was derived from a meta-analysis of up to 322,154 individuals, and the GWAS for waist circumference (WC) and waist-hip ratio (WHR) included 210,088 participants. RESULTS: MR showed that lifetime cannabis use (beta = - 0.018, 95 % confidence interval (CI) - 0.05-0.015; P-value = 0.279, Q-value = 0.279) and cannabis use disorder (beta = 0.023, 95 % CI 0.023-0.045; P-value = 0.034, Q-value = 0.092) were not associated with BMI. Considering WC and WHR as indicators of obesity, our findings did not support a causal association. Leave-one out analyses and pleiotropy-robust methods did not indicate bias in any of the estimates. CONCLUSIONS: Overall, the MR study provides little evidence that cannabis influences obesity related traits.