Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations.
- Authors
- Mathies, Laura D; Aliev, Fazil; COGA Investigators; Davies, Andrew G; Dick, Danielle M; Bettinger, Jill C
- Year
- 2017
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 28981154
- 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.
SWI/SNF chromatin remodeling complexesA. SWI/SNF complexes result from the combination of core (dark grey), common accessory (light grey), and unique accessory (stipple/PBAF or white/BAF) subunits. More than one gene encodes different versions of many of the subunits: the core ATPase subunit is encoded by SMARCA2 (BRM) or SMARCA4 (BRG1); BAF250 is encoded by ARID1A and ARID1B; BAF155 and BAF170 encode interchangeable core subunits; BAF45A is encoded by PHF10 and BAF45B-D are encoded by DPF1, DPF2 and DPF3; BAF53 is encoded by ACTL6A and ACTL6B; BAF60 is encoded by SMARCD1, SMARCD2, and SMARCD3; BCL7 is encoded by BCL7A, BCL7B, and BCL7C; BCL11 is encoded by BCL11A and BCL11B; SS18 and CREST are encoded by SS18 and SS18L1, respectively. B. BAF complexes purified from neural progenitors (npBAF) and differentiated neurons (nBAF) contain different SWI/SNF subunits; subunits that differ are highlighted with bold lines. npBAF contains BAF53A, BAF45A or BAF45D, and SS18. nBAF contains BAF53B, BAF45B, and CREST.
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| SWI/SNF complexes modulate gene expression and the development of physical dependence to ethanol. | Mathies LD et al. | — | 2026 | → |
| Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program. | Ashley-Koch AE et al. | — | 2023 | → |
| A Pan-Cancer Analysis of the Oncogenic Role of <i>BCL7B</i>: A Potential Biomarker for Prognosis and Immunotherapy. | Yang D et al. | — | 2022 | → |
| BCL7B is a potential novel diagnosis and prognosis biomarker for sarcomas using bioinformatics analysis. | Yang D et al. | — | 2021 | → |
| Mechanisms of Alcohol Addiction: Bridging Human and Animal Studies. | Kramer J et al. | — | 2020 | → |
| SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol. | Mathies LD et al. | — | 2020 | → |
| The Emerging Role of ATP-Dependent Chromatin Remodeling in Memory and Substance Use Disorders. | López AJ et al. | — | 2020 | → |
| Intrinsic Disorder of the BAF Complex: Roles in Chromatin Remodeling and Disease Development. | El Hadidy N et al. | — | 2019 | → |
| CREST in the Nucleus Accumbens Core Regulates Cocaine Conditioned Place Preference, Cocaine-Seeking Behavior, and Synaptic Plasticity. | Alaghband Y et al. | — | 2018 | → |
| Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes. | Alpsoy A et al. | — | 2018 | → |