Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior

J. E. Salvatore, A. C. Edwards, Jeanette McClintick, T. B. Bigdeli, A. Adkins, F. Aliev, Howard Edenberg, Tatiana Foroud, V. Hesselbrock, J. Kramer, John Nurnberger, M. Schuckit, J. A. Tischfield, Xiaoling Xuei, D. M. Dick

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Abstract

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 genomewide 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.

Original languageEnglish (US)
Article numbere558
JournalTranslational Psychiatry
Volume5
Issue number4
DOIs
StatePublished - Apr 28 2015

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Genome
Diagnostic and Statistical Manual of Mental Disorders
Genes
Alcoholism
Single Nucleotide Polymorphism
Antisocial Personality Disorder
Cocaine-Related Disorders
Brain
Case-Control Studies
Molecular Biology
Adenosine Triphosphate
Proteins

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Salvatore, J. E., Edwards, A. C., McClintick, J., Bigdeli, T. B., Adkins, A., Aliev, F., ... Dick, D. M. (2015). Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior. Translational Psychiatry, 5(4), [e558]. https://doi.org/10.1038/tp.2015.36

Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior. / Salvatore, J. E.; Edwards, A. C.; McClintick, Jeanette; Bigdeli, T. B.; Adkins, A.; Aliev, F.; Edenberg, Howard; Foroud, Tatiana; Hesselbrock, V.; Kramer, J.; Nurnberger, John; Schuckit, M.; Tischfield, J. A.; Xuei, Xiaoling; Dick, D. M.

In: Translational Psychiatry, Vol. 5, No. 4, e558, 28.04.2015.

Research output: Contribution to journalArticle

Salvatore, JE, Edwards, AC, McClintick, J, Bigdeli, TB, Adkins, A, Aliev, F, Edenberg, H, Foroud, T, Hesselbrock, V, Kramer, J, Nurnberger, J, Schuckit, M, Tischfield, JA, Xuei, X & Dick, DM 2015, 'Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior', Translational Psychiatry, vol. 5, no. 4, e558. https://doi.org/10.1038/tp.2015.36
Salvatore, J. E. ; Edwards, A. C. ; McClintick, Jeanette ; Bigdeli, T. B. ; Adkins, A. ; Aliev, F. ; Edenberg, Howard ; Foroud, Tatiana ; Hesselbrock, V. ; Kramer, J. ; Nurnberger, John ; Schuckit, M. ; Tischfield, J. A. ; Xuei, Xiaoling ; Dick, D. M. / Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior. In: Translational Psychiatry. 2015 ; Vol. 5, No. 4.
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abstract = "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 genomewide 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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AU - Adkins, A.

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AU - Nurnberger, John

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AU - Xuei, Xiaoling

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