The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study

Post-Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. Methods: Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (rg) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). Results: ADHD and PTSD had consistent rg (rg range, 0.43–0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186–0.552; p = 7.68 × 10−5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10−4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98–3.53). Conclusions: Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.

Original languageEnglish (US)
Pages (from-to)362-369
Number of pages8
JournalBiological Psychiatry
Volume93
Issue number4
DOIs
StatePublished - Feb 15 2023

Keywords

  • ADHD
  • Causal inference
  • Comorbidities
  • Epidemiology
  • Genome-wide association study
  • PTSD
  • Genome-Wide Association Study
  • Humans
  • Stress Disorders, Post-Traumatic/genetics
  • Mendelian Randomization Analysis
  • Attention Deficit Disorder with Hyperactivity/epidemiology
  • Siblings

ASJC Scopus subject areas

  • Biological Psychiatry

Fingerprint

Dive into the research topics of 'The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study'. Together they form a unique fingerprint.

Cite this