Genome-wide association study of antisocial personality disorder

Area of Science:

• Psychiatry
• Genetics
• Neuroscience

Background:

• Antisocial personality disorder (ASPD) pathophysiology is poorly understood.
• Genetic factors account for approximately 50% of ASPD liability, but specific genes are largely unknown.
• Consistent biological findings include reduced frontal cortex gray matter volume.

Purpose of the Study:

• To investigate the genetic background of antisocial personality disorder (ASPD).
• To identify specific genetic variants associated with ASPD through a genome-wide association study (GWAS).

Main Methods:

• Conducted a genome-wide association study (GWAS) and replication analysis in Finnish criminal offenders with ASPD.
• Analyzed single-nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region and at 6p21.2.
• Utilized imputation of HLA alleles and functional analysis of gene expression quantitative trait loci (eQTLs) in brain tissue.

Main Results:

• Suggestive associations found at 6p21.2 and 6p21.32 (HLA region).
• Independent association with HLA allele DRB1*01:01 identified.
• Replicated two polymorphisms at the 6p21.2 LINC00951-LRFN2 gene region, with rs4714329 reaching genome-wide significance (P=1.6 × 10⁻⁹).
• The risk allele rs4714329 associated with antisocial traits and showed eQTL associations with LINC00951 and LRFN2 in the cerebellum, with both genes expressed in the frontal cortex.

Conclusions:

• This study presents the first genome-wide significant and replicable genetic findings for any personality disorder.
• Identified genetic variants, particularly rs4714329 near LINC00951-LRFN2, associated with ASPD.
• Findings suggest a potential genetic link involving frontal cortex function and ASPD pathophysiology.