Copy Number Variations in 6q14.1 and 5q13.2 are Associated with Alcohol Dependence

Background: Excessive alcohol use is the third leading cause of preventable death and is highly correlated with alcohol dependence, a heritable phenotype. Many genetic factors for alcohol depen-dence have been found, but many remain unknown. In search of additional genetic factors, we exam-ined the association between Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition (DSM-IV) alcohol dependence and all common copy number variations (CNVs) with good reliability in the Study of Addiction: Genetics and Environment (SAGE). Methods: All participants in SAGE were interviewed using the Semi-Structured Assessment for the Genetics of Alcoholism, as a part of 3 contributing studies. A total of 2,610 non-Hispanic European American samples were genotyped on the Illumina Human 1M array. We performed CNV calling by CNVPartition, PennCNV, and QuantiSNP, and only CNVs identified by all 3 software programs were examined. Association was conducted with the CNV (as a deletion/duplication) as well as with probes in the CNV region. Quantitative polymerase chain reaction (qPCR) was used to validate the CNVs in the laboratory. Results: CNVs in 6q14.1 (p = 1.04 9 10!6) and 5q13.2 (p = 3.37 9 10!4) were significantly associ-ated with alcohol dependence after adjusting multiple tests. On chromosome 5q13.2, there were multi