Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations

COGA Investigators

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2033-2040
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume41
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Chromatin Assembly and Disassembly
Alcoholism
Chromatin
Sucrose
Alcohols
Population
Genes
Proteins
Biological Phenomena
Adolescent Behavior
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Testing
Genetics

Keywords

  • Alcohol Dependence
  • Antisocial Behavior
  • Chromatin Remodeling
  • Collaborative Study on the Genetics of Alcoholism
  • Externalizing
  • Switching Defective/Sucrose Nonfermenting

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

@article{3dab784f7a9a45e7814fa5fcd41fb554,
title = "Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations",
abstract = "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.",
keywords = "Alcohol Dependence, Antisocial Behavior, Chromatin Remodeling, Collaborative Study on the Genetics of Alcoholism, Externalizing, Switching Defective/Sucrose Nonfermenting",
author = "{COGA Investigators} and Mathies, {Laura D.} and Fazil Aliev and Davies, {Andrew G.} and Dick, {Danielle M.} and Bettinger, {Jill C.} and B. Porjesz and V. Hesselbrock and H. Edenberg and Howard Edenberg and J. Nurnberger and John Nurnberger and Tatiana Foroud and J. Kramer and B. Porjesz and L. Bierut and J. Rice and K. Bucholz and A. Agrawal and M. Schuckit and J. Tischfield and A. Brooks and L. Almasy and A. Goate and R. Taylor and Jeanette McClintick and J. McClintick and Xiaoling Xuei and X. Xuei and Y. Liu and Sean O'Connor and S. O'Connor and M. Plawecki and S. Lourens and G. Chan and J. Meyers and D. Chorlian and C. Kamarajan and A. Pandey and J. Zhang and Wang, {J. C.} and M. Kapoor and S. Bertelsen and A. Anokhin and V. McCutcheon and S. Saccone and J. Salvatore and B. Cho and M. Kos and A. Parsian and M. Reilly",
year = "2017",
month = "12",
day = "1",
doi = "10.1111/acer.13514",
language = "English (US)",
volume = "41",
pages = "2033--2040",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "12",

}

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 - Edenberg, Howard

AU - Nurnberger, J.

AU - Nurnberger, John

AU - Foroud, Tatiana

AU - Kramer, J.

AU - Porjesz, B.

AU - Bierut, L.

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 - McClintick, Jeanette

AU - McClintick, J.

AU - Xuei, Xiaoling

AU - Xuei, X.

AU - Liu, Y.

AU - O'Connor, Sean

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.

PY - 2017/12/1

Y1 - 2017/12/1

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

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U2 - 10.1111/acer.13514

DO - 10.1111/acer.13514

M3 - Article

C2 - 28981154

AN - SCOPUS:85032587029

VL - 41

SP - 2033

EP - 2040

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 12

ER -