Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations
Küçük Resim Yok
Tarih
2017
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
BackgroundTesting 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. MethodsWe 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]). ResultsWe 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. ConclusionsWe 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.
Açıklama
Anahtar Kelimeler
Alcohol Dependence, Switching Defective, Sucrose Nonfermenting, Collaborative Study on the Genetics of Alcoholism, Chromatin Remodeling, Externalizing, Antisocial Behavior
Kaynak
Alcoholism-Clinical and Experimental Research
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
41
Sayı
12
