Abstract
Alcohol dependence is a heritable disorder, yet its genetic basis and underlying mechanisms remain poorly understood, especially in Chinese population. In this study, we conducted gene-based and transcript-based association tests and found a significant association between ARVCF expression in the cortex and hippocampus of the brain and alcohol use in a cohort of 1,329 individuals with Chinese ancestry. Further analysis using the effective-median-based Mendelian randomization framework for inferring the causal genes (EMIC) revealed a causal relationship between ARVCF expression in the frontal cortex and alcohol use. Moreover, leveraging extensive European alcohol dependence data, our gene association tests and EMIC analysis showed that ARVCF expression in the nucleus accumbens was significantly associated with alcohol dependence. Finally, animal studies indicated that Arvcf knockout mice lacked conditioned place preference for alcohol. Together, our combined human genetic and animal studies indicate that ARVCF plays a crucial role in alcohol dependence.