Testing Bidirectional Genetic Links Between ADHD and the Big Five Personality Traits
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Attention Deficit Hyperactivity Disorder (ADHD) frequently co-occurs with distinct personality profiles, but whether ADHD shapes personality (scar model) or personality influences the development of ADHD (vulnerability model) remains unclear. Leveraging genome-wide association study (GWAS) data, we examined directional associations between ADHD and the Big Five personality traits (Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness). We estimated genetic correlations and conducted bidirectional two-sample Mendelian Randomization (MR) analyses between ADHD and the Big Five. Robustness was evaluated using multiple sensitivity tests, including MR-CAUSE, which accounts for correlated and uncorrelated pleiotropy, and colocalization analyses on fine-mapped variants. Higher genetic liability to Neuroticism and Extraversion, alongside lower liability to Conscientiousness, increased ADHD risk, consistent with the vulnerability model. Conversely, ADHD genetic liability was associated with lower Agreeableness, supporting the scar model. Associations were generally robust across sensitivity analyses, with MR-CAUSE supporting the Neuroticism and Agreeableness associations and colocalization providing variant-level support for associations between ADHD and Neuroticism, Conscientiousness, and Agreeableness. These findings provide early, population-level insight into personality-related vulnerability to ADHD and motivate further work on the role of personality traits in ADHD risk.
Source: medRxiv
Institutions: Centre National de la Recherche Scientifique, Inserm, Université Paris Sciences et Lettres, École Normale Supérieure - PSL, Centre Hospitalier Universitaire de Montpellier, Centre de recherche en Epidémiologie et Santé des Populations, Laboratoire de Sciences Cognitives et Psycholinguistique, École des hautes études en sciences sociales, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Corentin-Celton, Institut de Psychiatrie et Neurosciences de Paris, Université Paris-Est Créteil, Fondation FondaMental, Hôpitaux Universitaires Henri-Mondor, Institut Mondor de Recherche Biomédicale, Hôpitaux Universitaires de Strasbourg, Neuroscience et Psychiatrie Translationnelle de Strasbourg, Université de Strasbourg, Centre Hospitalier de Versailles, Institut Pasteur, Centre Hospitalier Sainte-Anne, GHU Paris psychiatrie & neurosciences, NeuroDiderot, McGill University, Michigan State University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7220895970