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

Laura D Mathies; Fazil Aliev; Andrew G Davies; Danielle M Dick; Jill C Bettinger; Collaborative Study on the Genetics of Alcoholism (COGA) Investigators

doi:10.1111/acer.13514

Back

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

Journal article

Peer reviewed

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

Laura D Mathies, Fazil Aliev, Andrew G Davies, Danielle M Dick, Jill C Bettinger and Collaborative Study on the Genetics of Alcoholism (COGA) Investigators

Alcoholism, clinical and experimental research, Vol.41(12), pp.2033-2040

12/2017

DOI: 10.1111/acer.13514

PMCID: PMC5711565

PMID: 28981154

View Online

Abstract

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. 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]). 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. 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.

Chromatin Remodeling

Externalizing

Switching Defective/Sucrose Nonfermenting

Alcohol Dependence

Collaborative Study on the Genetics of Alcoholism

Antisocial Behavior

Details

Title: Subtitle: Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations
Creators: Laura D Mathies - Virginia Commonwealth University
Fazil Aliev - Virginia Commonwealth University
Andrew G Davies - Virginia Commonwealth University
Danielle M Dick - Virginia Commonwealth University
Jill C Bettinger - Virginia Commonwealth University
Collaborative Study on the Genetics of Alcoholism (COGA) Investigators
Contributors: Samuel Kuperman (Contributor) - University of Iowa, Psychiatry
Resource Type: Journal article
Publication Details: Alcoholism, clinical and experimental research, Vol.41(12), pp.2033-2040
DOI: 10.1111/acer.13514
PMID: 28981154
PMCID: PMC5711565
NLM abbreviation: Alcohol Clin Exp Res
ISSN: 0145-6008
eISSN: 1530-0277
Publisher: Wiley
Grant note: P20 AA017828 / NIAAA NIH HHS R01 AA024482 / NIAAA NIH HHS R37 AA011408 / NIAAA NIH HHS UL1 RR031990 / NCRR NIH HHS K02 AA018755 / NIAAA NIH HHS R01 AA016837 / NIAAA NIH HHS U10 AA008401 / NIAAA NIH HHS P50 AA022537 / NIAAA NIH HHS
Language: English
Date published: 12/2017
Academic Unit: Psychiatry
Record Identifier: 9984293657602771

Metrics

5 Record Views

12 Times Cited - Web of Science

See more details