TY - JOUR
T1 - Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations
AU - COGA Investigators
AU - Mathies, Laura D.
AU - Aliev, Fazil
AU - Davies, Andrew G.
AU - Dick, Danielle M.
AU - Bettinger, Jill C.
AU - Porjesz, B.
AU - Hesselbrock, V.
AU - Edenberg, H.
AU - Bierut, L.
AU - Nurnberger, J.
AU - Foroud, T.
AU - Kuperman, S.
AU - Kramer, J.
AU - Rice, J.
AU - Bucholz, K.
AU - Agrawal, A.
AU - Schuckit, M.
AU - Tischfield, J.
AU - Brooks, A.
AU - Almasy, L.
AU - Goate, A.
AU - Taylor, R.
AU - Bauer, L.
AU - McClintick, J.
AU - Wetherill, L.
AU - Xuei, X.
AU - Liu, Y.
AU - Lai, D.
AU - O'Connor, S.
AU - Plawecki, M.
AU - Lourens, S.
AU - Chan, G.
AU - Meyers, J.
AU - Chorlian, D.
AU - Kamarajan, C.
AU - Pandey, A.
AU - Zhang, J.
AU - Wang, J. C.
AU - Kapoor, M.
AU - Bertelsen, S.
AU - Anokhin, A.
AU - McCutcheon, V.
AU - Saccone, S.
AU - Salvatore, J.
AU - Cho, B.
AU - Kos, M.
AU - Parsian, A.
AU - Reilly, M.
N1 - Funding Information:
We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). The authors declare that they have no conflicts of interest. We would like to thank the VCU students for making this study a success, as well as the many VCU faculty, students, and staff who contributed to the design and implementation of the project. Spit for Science: The VCU Student Survey has been supported by Virginia Commonwealth University, P20 AA017828, R37AA011408, K02AA018755 (to DMD), and P50 AA022537 from the National Institute on Alcohol Abuse and Alcoholism, and UL1RR031990 from the National Center for Research Resources and National Institutes of Health Roadmap for Medical Research. These funding sources had no role in the analysis or interpretation of the data, writing of the manuscript, or the decision to submit the study for publication. JCB, LDM, and AGD are supported by NIH R01AA024482 and P50AA022537.
Funding Information:
We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Con-neally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). The authors declare that they have no conflicts of interest.
Funding Information:
We would like to thank the VCU students for making this study a success, as well as the many VCU faculty, students, and staff who contributed to the design and implementation of the project. Spit for Science: The VCU Student Survey has been supported by Virginia Commonwealth University, P20 AA017828, R37AA011408, K02AA018755 (to DMD), and P50 AA022537 from the National Institute on Alcohol Abuse and Alcoholism, and UL1RR031990 from the National Center for Research Resources and National Institutes of Health Roadmap for Medical Research. These funding sources had no role in the analysis or interpretation of the data, writing of the manuscript, or the decision to submit the study for publication. JCB, LDM, and AGD are supported by NIH R01AA024482 and P50AA022537.
Publisher Copyright:
Copyright © 2017 by the Research Society on Alcoholism
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - Alcohol Dependence
KW - Antisocial Behavior
KW - Chromatin Remodeling
KW - Collaborative Study on the Genetics of Alcoholism
KW - Externalizing
KW - Switching Defective/Sucrose Nonfermenting
UR - http://www.scopus.com/inward/record.url?scp=85032587029&partnerID=8YFLogxK
U2 - 10.1111/acer.13514
DO - 10.1111/acer.13514
M3 - Article
C2 - 28981154
AN - SCOPUS:85032587029
SN - 0145-6008
VL - 41
SP - 2033
EP - 2040
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 12
ER -