Abstract
Objective: The objective of this study was to identify gene or genetic variants that would be responsible cannabis dependence in Thai people. Methods: We studied 144 cannabis dependent Thai people and 20 cannabis non-dependent people using whole exome sequencing and bioinformatic analysis. We used an integrated bioinformatic pipeline that combines two techniques: gene collapsing and disease module detection to identify potential genes involved in cannabis dependence. Results: Disease module detection analysis identified a single module of 53 genes with significantly higher rate of potentially damaging variant careers in cannabis dependent group compared to non-dependent group (Percentile Bootstrap’s p-value = 0.0000337, FDR=0.024). Of this module, we found that MYEF2 (Myelin Expression Factor 2; MIM 619395) was associated with cannabis dependence in our Thai cohort (Fisher’s Exact p-value = 0.0013, Odds ratio = 2.43(1.38-4.23), FDR = 0.04). MYEF2 is a single-stranded DNA-binding protein. Its role is to inhibit transcription of MBP (Myelin Basic Protein; MIM 15940) gene. MBP regulates maintenance of myeline structure. Conclusion: We propose for the first time based on our bioinformatic analyses that MYEF2 was associated with cannabis dependence.
