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Copy Number Variations in 6q14.1 and 5q13.2 are Associated with Alcohol Dependence
Author(s) -
Lin Peng,
Hartz Sarah M.,
Wang JenChyong,
Agrawal Arpana,
Zhang TianXiao,
McKenicholas,
Bucholz Kathleen,
Brooks Andrew I.,
Tischfield Jay A.,
Edenberg Howard J.,
Hesselbrock Victor M.,
Kramer John R.,
Kuperman Samuel,
Schuckit Marc A.,
Goate Alison M.,
Bierut Laura J.,
Rice John P.
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01758.x
Subject(s) - copy number variation , genetics , alcohol dependence , gene duplication , biology , snp array , medicine , gene , single nucleotide polymorphism , alcohol , genotype , genome , biochemistry
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 dependence have been found, but many remain unknown. In search of additional genetic factors, we examined the association between Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition (DSM‐IV) alcohol dependence and all common copy number variations ( CNV s) 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‐ H ispanic E uropean A merican samples were genotyped on the Illumina Human 1M array. We performed CNV calling by CNV Partition, P enn CNV , and Q uanti SNP , and only CNV s 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 (q PCR ) was used to validate the CNV s in the laboratory. Results CNVs in 6q14.1 ( p = 1.04 × 10 −6 ) and 5q13.2 ( p = 3.37 × 10 −4 ) were significantly associated with alcohol dependence after adjusting multiple tests. On chromosome 5q13.2, there were multiple candidate genes previously associated with various neurological disorders. The region on chromosome 6q14.1 is a gene desert that has been associated with mental retardation and language delay. The CNV in 5q13.2 was validated, whereas only a component of the CNV on 6q14.1 was validated by q PCR . Thus, the CNV on 6q14.1 should be viewed with caution. Conclusions This is the first study to show an association between DSM ‐IV alcohol dependence and CNV s. CNV s in regions previously associated with neurological disorders may be associated with alcohol dependence.