Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior.
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.
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
J E
JE
Salvatore
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
A C
AC
Edwards
Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA.
J N
JN
McClintick
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
T B
TB
Bigdeli
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
A
A
Adkins
1] Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA [2] Department of Statistics and Institute of Biotechnology, Ankara University, Ankara, Turkey.
F
F
Aliev
Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA.
H J
HJ
Edenberg
Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.
T
T
Foroud
Department of Psychiatry, University of Connecticut, Farmington, CT, USA.
V
V
Hesselbrock
Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
J
J
Kramer
Department of Psychiatry, Indiana University, Indianapolis, IN, USA.
J I
JI
Nurnberger
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
M
M
Schuckit
Department of Genetics, Rutgers University, Piscataway, NJ, USA.
J A
JA
Tischfield
Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA.
X
X
Xuei
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
D M
DM
Dick
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000437:Alcoholism / Q000235:genetics; D000987:Antisocial Personality Disorder / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D007370:Interferon Type I