Identification and validation of a novel gene ARVCF associated with alcohol dependence among Chinese population
Xiaoqiang Shi,
Yan Wang,
Zhongli Yang,
Wenji Yuan,
Ming D. Li
Affiliations
Xiaoqiang Shi
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
Yan Wang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
Zhongli Yang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
Wenji Yuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
Ming D. Li
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Research Center for Air Pollution and Health, Zhejiang University, Hangzhou 310058, China; Corresponding author
Summary: 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.
