Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior
Year: 2015
Type: article
Study design: Observational Study
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 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.
Source: Translational Psychiatry
DOI: 10.1038/tp.2015.36
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,290
Funders: State University of New York, Washington University in St. Louis, University of Connecticut, Johns Hopkins University, Texas Biomedical Research Institute, Alvin J. Siteman Cancer Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, SUNY Downstate Medical Center, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1114310655, Genes, Environments & Interventions: Understanding and Addressing Alcohol Misuse, Genetic influences on developmental heterogeneity of alcohol use disorder, G2146332128, G299873027, G4503763930, G5153300018, G5483271793, Genetically-informed designs of externalizing behavior and romantic relationships, JH/CIDR Genotyping for Genome-Wide Association Studies, G7093047072, Washington University Institute of Clinical and Translational Sciences, G7522350138, Washington University Institute of Clinical and Translational Sciences (UL1), G8267674335, Cancer Center Support Grant, Collaborative Study on the Genetics of Alcoholism (COGA).
OpenAlex ID: W1992593963