The Genetic Effect of Copy Number Variations on the Risk of Alcoholism in a Korean Population

Background:  Alcoholism, a chronic behavioral disorder characterized by excessive alcohol consumption, has been a leading cause of morbidity and premature death. This condition is believed to be influenced by genetic factors. As copy number variation (CNV) has been recently discovered in human genome, genomic diversity of human genome is more frequent than previously thought. Many studies have reported evidences that CNV is associated with the development of complex diseases. In this study, we hypothesized that CNV can predict the risk of alcoholism.Methods:  Using the Illumina HumanHap660W???Quad BeadChip (∼660 k markers), genome???wide genotyping was performed to obtain signal and allelic intensities from 116 alcoholic cases and 1,022 healthy controls (total n = 1,138) in a Korean population. To identify alcoholism???associated CNV regions, we performed a genome???wide association analysis, using multivariate logistic regression model controlling for age and gender.Results:  We identified a total of 255,732 individual CNVs and 3,261 CNV regions (1,067 common CNV regions, frequency > 1%) in this study. Results from multivariate logistic regression showed that the chr20:61195302???61195978 regions were significantly associated with the risk of alcoholism after multiple corrections (p = 5.02E−05, pcorr = 0.04). Most of the identified variations in this study overlapped with the previously reported CNVs in the Database of Genomic Variants (95.3%). The identified CNVs, which encompassed 3,226 functional genes, were significantly enriched in the cellular part, in the membrane???bound organelle, in the cell part, in developmental processes, in cell communication, in neurological system process, in sensory perception of smell and chemical stimulus, and in olfactory receptor activity.Conclusions:  This is the first genome???wide association study to investigate the relationship between common CNV and alcoholism. Our results suggest that the newly identified CNV regions may contribute to the development of alcoholism.We thank Dr. KaiWang (Department of Genetics, University of Pennsylvania, and Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA) for providing useful perl scripts for CNV analyses. This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A080906)