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Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations
Author(s) -
Mathies Laura D.,
Aliev Fazil,
Davies Andrew G.,
Dick Danielle M.,
Bettinger Jill C.
Publication year - 2017
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/acer.13514
Subject(s) - genetics , alcohol dependence , single nucleotide polymorphism , swi/snf , biology , population , locus (genetics) , chromatin , gene , chromatin remodeling , genotype , alcohol , medicine , biochemistry , environmental health
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 SS 18L1, SMARCD 1 , BRD 7 , BCL7B , SMARCB 1 , and BCL 11A . In the S4S sample, ACTB , ARID 2 , BCL 11A , BCL 11B , BCL 7B , BCL 7C , DPF 2 , and DPF 3 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.