The largest study of genes and personality finds neuroticism’s genetic fingerprint on nearly every psychiatric diagnosis
STUDY: Schwaba T et al, Nature 2026
STUDY TYPE: Genome-wide association study (GWAS) meta-analysis
FUNDING: Independent
Background
Personality traits like neuroticism have long been linked to psychiatric illness, but it’s been unclear how much of that link is genetic versus shared upbringing. This is the largest genetic study of personality yet, built to answer that.
Here’s what neuroticism looks like. It’s helpful for patients to know if they have this temperament, as helps them understand their personal link between stress and depression, pointing the way to therapeutic approaches that prevent these traits from escalating (table from Difficult to Treat Depression).
The Neurotic Temperament |
| I get stressed out easily |
| I dislike myself |
| I worry about things |
| I have frequent mood swings |
| I often get angry or irritated |
| I panic easily |
| I am often down in the dumps |
| I am easily bothered by things |
| I have trouble relaxing |
| I am easily frustrated |
| I fear the worst |
| I am rarely calm under pressure |
| I feel threatened easily |
| I am filled with doubts about things |
The Study
- Meta-analysis of genome-wide association data across 46 cohorts, up to 1.14 million people, covering the Big Five traits.
- Included within-family analyses (up to 50,725 people) to separate genetic effects from shared environment.
- Tested genetic correlations with 85 traits, including 10 psychiatric disorders, using Mendelian randomization for causal direction.
Results
Every trait showed genetic overlap with psychopathology. Neuroticism carried more risk across nearly all mental illness, especially depression and anxiety, while agreeableness looked protective. There were also links to health: Higher conscientiousness predicted less obesity and smoking. These links held up within families, ruling out shared upbringing.
The genetics of personality were unusually consistent in this study, across geography, age, sex, and reporter. Among the five traits, agreeableness had the lowest genetic linkage.
The Big Five Traits
These are the five traits with the most robust research behind them. They occur on a spectrum, and people can have them or their opposite.
- Openness to experience: Creativity, curiosity, and an appreciation for new ideas and adventures. People high in openness like variety and learning, while those low in openness prefer routine and familiar things.
- Conscientiousness: Organization, self-discipline, responsibility, and goal-directed behavior. High scorers are thorough and mindful of deadlines, whereas low scorers can be more spontaneous or easily distracted.
- Extraversion: Measures where people get their energy and how they interact socially. Extraverts are outgoing, talkative, and energized by group settings, while introverts need quiet time alone to recharge.
- Agreeableness: Measures a person’s concern for social harmony, empathy, and cooperation. Highly agreeable individuals are trusting and kind, while low scorers may be more competitive, skeptical, or blunt.
- Neuroticism: Emotional reactivity and vulnerability to stress or negative emotions like anxiety and sadness. High scorers experience more emotional instability or mood swings, while low scorers tend to be calmer and more resilient.
In borderline personality, agreeableness and conscientiousness tends to be low, neuroticism and openness to experience high.
Limitations
Genetic scores explained only a modest share of any one person’s personality (9-13%). Samples mainly of European ancestry. Genetic correlation isn’t proof of a shared causal pathway, even when Mendelian randomization points that way.
Practice Implications
- Understanding temperament reveals weaknesses and strengths. Neuroticism, for example, can lead to accomplishments in creative work, when paired with openness to experience.
- Learn how low-conscientiousness is strongly linked to alcohol use disorder.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
