Variation in SWI/SNF chromatin remodeling complex proteins is associated with alcohol dependence and antisocial behavior in human populations

October 5, 2017

Mathies LD, Aliev F, COGA Investigators, Davies AG, Dick DM, Bettinger JC
Alcohol. Clin. Exp. Res. 2017 41(12): 2033-2040 doi: 10.1111/acer.13514. PMCID: PMC5711565

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.