Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders

Author:

Li Wenqianglong1,Zhou Hang23,Thygesen Johan H.14,Heydtmann Mathis56,Smith Iain7,Degenhardt Franziska8,Nöthen Markus9,Morgan Marsha Y.10,Kranzler Henry R.1112,Gelernter Joel2313,Bass Nicholas1,McQuillin Andrew1

Affiliation:

1. Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK

2. Department of Psychiatry, Yale School of Medicine, New Haven

3. Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA

4. Institute of Health Informatics, University College London, London, UK

5. Royal Alexandria Hospital, NHS Greater Glasgow and Clyde, Paisley, UK

6. Department of Gastroenterology, Dumfries & Galloway Royal Infirmary, Cargenbridge, Dumfries, Scotland

7. Substance misuse service, Mayfield Centre, St Ninians, Stirling, UK

8. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen

9. Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany

10. UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK

11. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine

12. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania

13. Departments of Genetics and Neuroscience, Yale University School of Medicine, New Haven, Connecticut, USA

Abstract

Introduction While progress has been made in determining the genetic basis of antisocial behaviour, little progress has been made for antisocial personality disorder (ASPD), a condition that often co-occurs with other psychiatric conditions including substance use disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. This study aims to improve the understanding of the genetic risk for ASPD and its relationship with other disorders and traits. Methods We conducted a genome-wide association study (GWAS) of the number of ASPD diagnostic criteria data from 3217 alcohol-dependent participants recruited in the UK (UCL, N = 644) and the USA (Yale-Penn, N = 2573). Results We identified rs9806493, a chromosome 15 variant, that showed a genome-wide significant association (Z-score = −5.501, P = 3.77 × 10−8) with ASPD criteria. rs9806493 is an eQTL for SLCO3A1 (Solute Carrier Organic Anion Transporter Family Member 3A1), a ubiquitously expressed gene with strong expression in brain regions that include the anterior cingulate and frontal cortices. Polygenic risk score analysis identified positive correlations between ASPD and smoking, ADHD, depression traits, and posttraumatic stress disorder. Negative correlations were observed between ASPD PRS and alcohol intake frequency, reproductive traits, and level of educational attainment. Conclusion This study provides evidence for an association between ASPD risk and SLCO3A1 and provides insight into the genetic architecture and pleiotropic associations of ASPD.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Biological Psychiatry,Psychiatry and Mental health,Genetics (clinical),Genetics

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