Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior
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Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case–control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702,P=5.77 × 10−7) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test,ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain.ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.
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Other published genome-wide association studies of antisocial phenotypes did not report genome-wide significant associations.
“none of the other published GWAS studies Tielbeek et al. 2012(Tielbeek et al., 2012) (QIMR, N=4816, continuous measure of adult antisocial behaviour), Salvatore et al. 2015(Salvatore et al., 2015) (COGA, N=1379, continuous measure of adult antisocial behaviour, part of the present meta-analysis), Viding et al. 2010(Viding et al., 2010) (TEDS, N=1186 (Ncases=593), psychopathic tendencies) and Derr”
From Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior (2017) · cites this paper as Salvatore et al., 2015
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Whittington, R., McGuire, J., & Peres, M. F. T. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139086486.007
Whittington, R., McGuire, J., & Peres, M. F. T. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139086486.012
Whittington, R., McGuire, J., & Peres, M. F. T. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139086486.011
Whittington, R., McGuire, J., & Peres, M. F. T. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139086486.008
Whittington, R., McGuire, J., & Peres, M. F. T. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139086486.003
Medikamente zur Behandlung von Persönlichkeits- und Verhaltensstörungen
Müller, M. J., & Benkert, O. (2016) · Springer eBooks · doi:10.1007/978-3-662-50333-1_11
Whittington, R., McGuire, J., & Peres, M. F. T. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139086486.014
Addressing the Associated Conditions of Drug and Alcohol Abuse
Kiefer, F., & Frischknecht, U. (2020) · doi:10.1002/9781119159322.ch39
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Çakıl, Y. D., Özünal, Z. G., İşeri, Ö. D., & Yurtçu, E. (2024) · Interdisciplinary cancer research · doi:10.1007/16833_2024_346
- Authors
- Salvatore, J. E., Edwards, A. C., McClintick, J. N., Bigdeli, T. B., Adkins, A., Aliev, F., Edenberg, H. J., Foroud, T., Hesselbrock, V, Kramer, J., Nurnberger, J. I., Schuckit, M., Tischfield, J. A., Xuei, X., & Dick, D. M.
- Affiliations
- Virginia Commonwealth University (US)
- Indiana University Indianapolis (US)
- University of Connecticut (US)
- University of Iowa (US)
- University of California San Diego (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Salvatore, J E
- Dick, D M
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2015-04-28
- Volume
- 5
- Issue
- 4
- Pages
- e558-e558
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4462601
- OpenAlex
- W1992593963
- Cited by
- 42
- References
- 58
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 17 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 5
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion, cc-by)
- VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- State University of New York
- Washington University in St. Louis
- University of Connecticut
- Johns Hopkins University (HHSN268200782096C, U01HG004438)
- Texas Biomedical Research Institute
- Alvin J. Siteman Cancer Center (CA91842, #P30 CA91842, UL1RR024992)
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health (HHSN268200782096C, UL1TR000448, CA91842)
- SUNY Downstate Medical Center
- National Institute on Alcohol Abuse and Alcoholism (Grant U10AA008401, K02AA018755, K01AA021399, HHSN268200782096C, F32AA022269, U10AA008401)
- National Institute on Drug Abuse (Grant U10AA008401, HHSN268200782096C)
- National Human Genome Research Institute (U01HG004438, HHSN268200782096C)
- National Cancer Institute (P30 CA 91842, CA91842, P30CA091842)
- National Center for Research Resources (UL1RR024992, P30 CA91842)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- P-glycoprotein, MDR1, immune-related genes, alcoholism, cocaine dependence, antisocial personality disorder, brain gene expression, externalizing problems, genetic risk, single nucleotide polymorphisms
- MeSH terms
- Adult, Alcoholism, Antisocial Personality Disorder, Brain, Female, Humans, Interferon Type I, Male, Case-Control Studies, ATP Binding Cassette Transporter, Subfamily B, Cocaine-Related Disorders, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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