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Alcohol Clin Exp Res. 2017 Dec;41(12):2033-2040. doi: 10.1111/acer.13514. Epub 2017 Oct 27.

Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations.

Author information

1
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia.
2
Department of Psychology, Virginia Commonwealth University, Richmond, Virginia.
3
Karabuk University, Karabuk, Turkey.
4
Virginia Commonwealth University Alcohol Research Center, Richmond, Virginia.
5
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.

Abstract

BACKGROUND:

Testing for direct gene or single nucleotide polymorphism replication of association across studies may not capture the true importance of a candidate locus; rather, we suggest that relevant replication across studies may be found at the level of a biological process. We previously observed that variation in 2 members of the switching defective/sucrose nonfermenting (SWI/SNF) chromatin remodeling complex is associated with alcohol dependence (AD) in the Irish Affected Sib Pair Study for Alcohol Dependence. Here, we tested for association with alcohol-related outcomes using a set of genes functioning in the SWI/SNF complex in 2 independent samples.

METHODS:

We used a set-based analysis to examine the 29 genes of the SWI/SNF complex for evidence of association with (i) AD in the adult Collaborative Study on the Genetics of Alcoholism (COGA) case-control sample and (ii) antisocial behavior, hypothesized to be a genetically related developmental precursor, in a younger population sample (Spit for Science [S4S]).

RESULTS:

We found evidence for association of the SWI/SNF complex with AD in COGA (p = 0.0435) and more general antisocial behavior in S4S (p = 0.00026). The genes that contributed most strongly to the signal in COGA were SS18L1, SMARCD1, BRD7, BCL7B, SMARCB1, and BCL11A. In the S4S sample, ACTB, ARID2, BCL11A, BCL11B, BCL7B, BCL7C, DPF2, and DPF3 all contributed strongly to the signal.

CONCLUSIONS:

We detected associations between the SWI/SNF complex and AD in an adult population selected from treatment-seeking probands and antisocial behavior in an adolescent population sample. This provides strong support for a role for SWI/SNF in the development of alcohol-related problems.

KEYWORDS:

Alcohol Dependence; Antisocial Behavior; Chromatin Remodeling; Collaborative Study on the Genetics of Alcoholism; Externalizing; Switching Defective/Sucrose Nonfermenting

PMID:
28981154
PMCID:
PMC5711565
DOI:
10.1111/acer.13514
[Indexed for MEDLINE]
Free PMC Article

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