Identification and validation of a novel gene ARVCF associated with alcohol dependence among Chinese population

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 <i>ARVCF</i> 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 <i>ARVCF</i> expression in the frontal cortex and alcohol use. Moreover, leveraging extensive European alcohol dependence data, our gene association tests and EMIC analysis showed that <i>ARVCF</i> expression in the nucleus accumbens was significantly associated with alcohol dependence. Finally, animal studies indicated that <i>Arvcf</i> knockout mice lacked conditioned place preference for alcohol. Together, our combined human genetic and animal studies indicate that <i>ARVCF</i> plays a crucial role in alcohol dependence.