Association between lifetime cannabis use and brain imaging phenotypes in UK Biobank
Poster No:
2279
Submission Type:
Abstract Submission
Authors:
Saba Ishrat1, Daniel F. Levey2, Joel Gelernter2, Klaus P. Ebmeier1, Anya Topiwala1
Institutions:
1University of Oxford, Oxford, UK, 2Yale University School of Medicine, New Haven, CT, USA
First Author:
Co-Author(s):
Introduction:
In the past decade cannabis use has increased worldwide following its legalization for medical and recreational purposes. This legalization has occurred without a comprehensive understanding of the potential effect of cannabis on the brain. Cannabis use during adolescence and young adulthood has shown a significant association with brain structure and functional connectivity. However, despite a rapid increase in cannabis use among older adults, its relationship with brain structure and function in this population remains understudied. There are reports of adverse cannabis effects on neuro-cognitive performance, brain structure and function. Whether there is a safe threshold of cannabis use is unknown.
Here, we investigate associations between cannabis use and a rich set of measures of structure and function across the brain in a large cohort of older adults. We employ both hypothesis-driven and agnostic approaches, and triangulate our observational findings with Mendelian randomization, a method to investigate causal relationships.
Here, we investigate associations between cannabis use and a rich set of measures of structure and function across the brain in a large cohort of older adults. We employ both hypothesis-driven and agnostic approaches, and triangulate our observational findings with Mendelian randomization, a method to investigate causal relationships.
Methods:
We examined 3,641 lifetime cannabis users (mean age = 61.00 years, standard deviation (SD) = 7.16) and 12,255 controls (mean age = 64.49 years, SD = 7.58) from the UK Biobank. Insufficient data were available on cannabis use disorders in the UK Biobank to perform an analysis. All statistical analysis was performed in R (version 4.0.0) and visualizations were performed in MATLAB (version R2018_a). Brain structure and functional connectivity were measured using multiple imaging-derived phenotypes (IDPs). Associations with cannabis use were assessed using multiple linear regression while controlling for potential confounders.
Additionally, we conducted two-sample Mendelian randomization analysis using genome-wide association study (GWAS) summary statistics data based on two different cannabis phenotypes: 'cannabis dependence or abuse' and 'lifetime cannabis use'. The summary statistics for the brain IDPs was obtained from GWAS performed by the UK Biobank. We used TwoSampleMR in an R package to investigate whether significant observed associations between cannabis use and brain IDPs were causal.
Additionally, we conducted two-sample Mendelian randomization analysis using genome-wide association study (GWAS) summary statistics data based on two different cannabis phenotypes: 'cannabis dependence or abuse' and 'lifetime cannabis use'. The summary statistics for the brain IDPs was obtained from GWAS performed by the UK Biobank. We used TwoSampleMR in an R package to investigate whether significant observed associations between cannabis use and brain IDPs were causal.
Results:
Out of 3,921 brain IDPs, cannabis use was significantly associated with 40 brain IDPs after FDR correction (0.05%, p = 0.009) (Figure 1). The strongest associations were with measures of white matter microstructure. Most significant associations identified in the DTI metrics were found in the genu and body of the corpus callosum, demonstrating lower fractional anisotropy (FA) and higher mean diffusivity (MD). A wide range of associations was observed across various rsFC analyses, particularly indicating either weaker or stronger connectivity between multiple networks. These networks predominantly included brain regions associated with the default mode, central executive network. We did not replicate previously observed associations between cannabis use and grey matter volume in the hippocampus and amygdala.
Furthermore, bidirectional two-sample Mendelian randomization analyses found no support for a causal relationship between either cannabis use or cannabis dependence and brain structure or function.
Furthermore, bidirectional two-sample Mendelian randomization analyses found no support for a causal relationship between either cannabis use or cannabis dependence and brain structure or function.
Conclusions:
Lifetime cannabis use is associated with several measures of brain structure and function in later life, particularly in the corpus callosum. Genetic analysis did not provide support for these associations resulting from causal relationships, suggesting residual confounding may be responsible.
Genetics:
Genetic Association Studies 2
Novel Imaging Acquisition Methods:
Anatomical MRI 1
BOLD fMRI
Diffusion MRI
Keywords:
MRI
Other - Cannabis use, cannabis dependence, brain structure, brain function, mendelian randomization
1|2Indicates the priority used for review
Provide references using author date format
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