Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence

Peng Lin; Sarah M Hartz; Jen-Chyong Wang; Arpana Agrawal; Tian-Xiao Zhang; Nicholas McKenna; Kathleen Bucholz; Andrew I Brooks; Jay A Tischfield; Howard J Edenberg; Victor M Hesselbrock; John R Kramer; Samuel Kuperman; Marc A Schuckit; Alison M Goate; Laura J Bierut; John P Rice; COGA Collaborators

doi:10.1111/j.1530-0277.2012.01758.x

Back

Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence

Journal article

Peer reviewed

Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence

Peng Lin, Sarah M Hartz, Jen-Chyong Wang, Arpana Agrawal, Tian-Xiao Zhang, Nicholas McKenna, Kathleen Bucholz, Andrew I Brooks, Jay A Tischfield, Howard J Edenberg, …

Alcoholism, clinical and experimental research, Vol.36(9), pp.1512-1518

09/2012

DOI: 10.1111/j.1530-0277.2012.01758.x

PMCID: PMC3436997

PMID: 22702843

View Online

Abstract

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 (CNVs) with good reliability in the Study of Addiction: Genetics and Environment (SAGE). 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. 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 qPCR. Thus, the CNV on 6q14.1 should be viewed with caution. This is the first study to show an association between DSM-IV alcohol dependence and CNVs. CNVs in regions previously associated with neurological disorders may be associated with alcohol dependence.

Polymerase Chain Reaction

Diagnostic and Statistical Manual of Mental Disorders

Genome-Wide Association Study

Reproducibility of Results

Humans

Alcohol Drinking - psychology

European Continental Ancestry Group

Genotype

Male

Alcohol Drinking - genetics

DNA Copy Number Variations

Age of Onset

Adult

Alcoholism - genetics

Female

Polymorphism, Single Nucleotide

Quality Control

Details

Title: Subtitle: Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence
Creators: Peng Lin - Department of Psychiatry, Washington University, St. Louis, Missouri, USA
Sarah M Hartz
Jen-Chyong Wang
Arpana Agrawal
Tian-Xiao Zhang
Nicholas McKenna
Kathleen Bucholz
Andrew I Brooks
Jay A Tischfield
Howard J Edenberg
Victor M Hesselbrock
John R Kramer
Samuel Kuperman
Marc A Schuckit
Alison M Goate
Laura J Bierut
John P Rice
COGA Collaborators
Resource Type: Journal article
Publication Details: Alcoholism, clinical and experimental research, Vol.36(9), pp.1512-1518
DOI: 10.1111/j.1530-0277.2012.01758.x
PMID: 22702843
PMCID: PMC3436997
NLM abbreviation: Alcohol Clin Exp Res
ISSN: 0145-6008
eISSN: 1530-0277
Publisher: Wiley; England
Grant note: U01 HG004422 / NHGRI NIH HHS U01HG004438 / NHGRI NIH HHS R01 DA019963 / NIDA NIH HHS U01 HG004446 / NHGRI NIH HHS N01DA47745 / NIDA NIH HHS U10 AA008401 / NIAAA NIH HHS U01 HG004438 / NHGRI NIH HHS K08 DA032680 / NIDA NIH HHS R01 DA013423 / NIDA NIH HHS U24 MH068457 / NIMH NIH HHS HHSN268200782096C / NHGRI NIH HHS U24 MH068457-10 / NIMH NIH HHS U10 AA008401-24 / NIAAA NIH HHS HHSN268200782096C / NHLBI NIH HHS KL2 TR000450 / NCATS NIH HHS P01 CA089392 / NCI NIH HHS
Language: English
Date published: 09/2012
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003483702771

Metrics

22 Record Views

13 Times Cited - Web of Science

See more details