🧬 biology

Testing Bidirectional Genetic Links Between ADHD and the Big Five Personality Traits

Using bidirectional Mendelian Randomization and genomic data, this study reveals that higher genetic liability for Neuroticism and Extraversion and lower liability for Conscientiousness increase ADHD risk (supporting a vulnerability model), while ADHD genetic liability subsequently reduces Agreeableness (supporting a scar model).

Original authors: Hugo Peyre, Nicolas HOERTEL, baptiste pignon, Sebastien Weibel, Speranza Mario, Boris Chaumette, Schwaba Ted, Camille Michèle Williams

Published 2026-10-14

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Hugo Peyre, Nicolas HOERTEL, baptiste pignon, Sebastien Weibel, Speranza Mario, Boris Chaumette, Schwaba Ted, Camille Michèle Williams

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ⚕️ This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer

For decades, parents and clinicians have watched children struggle with attention, hyperactivity, and impulsivity, wondering if these behaviors are the result of a specific personality or if the disorder itself reshapes who the child becomes. This question sits at the intersection of two major fields of human study: the diagnosis of attention deficit hyperactivity disorder, a condition defined by persistent difficulties in focusing and controlling impulses, and the measurement of personality, which describes stable patterns in how people think, feel, and act. Scientists have long known that these two areas overlap; people with the disorder often score differently on standard personality measures than those without it. However, the direction of the influence has remained a mystery. Does a child's natural temperament make them more likely to develop the disorder, or does the experience of living with the disorder leave a lasting mark on their personality? Resolving this direction is crucial because it changes how we understand the roots of the condition and how we might support those who have it.

To answer this, a team of researchers turned to the most detailed genetic maps available, using a method that treats DNA variations as natural experiments to trace cause and effect. They focused on the five broad dimensions of personality that psychologists use to describe human character: neuroticism, which reflects a tendency toward stress and emotional instability; agreeableness, which measures trust and kindness; extraversion, capturing sociability and energy; conscientiousness, the drive for order and goal-directed behavior; and openness, the willingness to explore new ideas. By analyzing genetic data from hundreds of thousands of people, the researchers could see if the genetic risk for the disorder pushed personality in a certain direction, or if the genetic makeup for specific personality traits pushed a person toward the disorder.

The study found that the relationship is not a one-way street, but rather a set of specific, directional links that vary depending on the trait. The evidence strongly suggests that certain personality traits act as a vulnerability, increasing the likelihood that a person will develop the disorder. Specifically, a genetic tendency toward higher neuroticism and higher extraversion, combined with a genetic tendency toward lower conscientiousness, was found to increase the risk of the disorder. This supports the idea that these personality characteristics can make a person more susceptible to the condition. In contrast, the study found that the disorder itself appears to shape personality in a more limited way. The genetic liability for the disorder was linked to a decrease in agreeableness, suggesting that living with the condition may leave a lasting "scar" on a person's ability to be trusting and cooperative, rather than the other way around.

The researchers reached these conclusions by examining the genetic code of over 38,000 individuals diagnosed with the disorder and hundreds of thousands of others, comparing their DNA against large datasets of personality traits. They used a rigorous statistical approach that filters out coincidental genetic links to isolate true causal pathways. When they looked at neuroticism, the data showed a robust effect where higher genetic risk for emotional stress led to a higher risk of the disorder. Similarly, a genetic predisposition for lower conscientiousness, which involves struggles with organization and self-control, was a clear risk factor. The link with extraversion was also present, indicating that a natural tendency toward high energy and sociability could contribute to the risk profile. However, when the researchers tested the reverse—whether the disorder caused changes in these traits—the evidence was weak or non-existent for neuroticism, extraversion, and conscientiousness.

The most significant finding regarding the disorder's impact on personality was its effect on agreeableness. The analysis showed that having a genetic risk for the disorder leads to lower scores in agreeableness, meaning a person is less likely to be trusting, compassionate, or cooperative. This supports the "scar model," where the difficulties and social challenges of the disorder alter a person's personality over time. The researchers also looked at openness to experience and found no significant genetic link in either direction, suggesting that curiosity and a love for new ideas are largely independent of the disorder. To ensure these findings were not just statistical flukes, the team ran multiple checks, including tests to see if the same genetic variants were driving both traits by chance. These checks confirmed the results, particularly for the links between neuroticism, conscientiousness, and the disorder, as well as the link between the disorder and lower agreeableness.

While the study provides a clear picture of how these traits interact at a genetic level, the authors note that the resolution of their genetic maps has limits. They could pinpoint specific shared genetic signals for some traits, such as a region on chromosome 7 involving a gene linked to brain development that connects the disorder with agreeableness. However, for other traits, the genetic signals were too broad to identify a single shared cause with absolute precision. Despite these technical limits, the overall pattern is consistent: personality traits like high neuroticism and low conscientiousness appear to set the stage for the disorder, while the disorder itself seems to erode agreeableness. This distinction helps move the conversation beyond simple correlation, offering a clearer view of which aspects of personality are risk factors and which are consequences, a nuance that could eventually inform how clinicians approach prevention and support.

Technical Summary: Testing Bidirectional Genetic Links Between ADHD and the Big Five Personality Traits

Problem Statement
Attention Deficit Hyperactivity Disorder (ADHD) frequently co-occurs with distinct personality profiles, yet the directionality of this relationship remains unresolved. Two competing frameworks attempt to explain this link: the vulnerability model, which posits that specific personality traits increase the risk of developing ADHD, and the scar model, which suggests that the experience of ADHD leaves a lasting "scar" on an individual's personality. While phenotypic associations are well-documented (e.g., higher Neuroticism and lower Conscientiousness in ADHD), previous studies have been limited by a lack of statistical power and an inability to distinguish between causal effects, shared genetic liability, or environmental confounding. This study aims to clarify the directional genetic architecture between ADHD and the five Big Five personality traits (Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness) using large-scale genomic data.

Methodology
The authors leveraged the largest available Genome-Wide Association Study (GWAS) summary statistics for ADHD (38,691 cases, 186,843 controls) and the Big Five traits (approximately 500,000 to 1 million participants) from European ancestry groups. The analytical pipeline included:

Genetic Correlation: Linkage Disequilibrium Score Regression (LDSC) was used to estimate genetic correlations ( $r_g$ ) between ADHD and each personality trait.
Bidirectional Mendelian Randomization (MR): Two-sample MR analyses were conducted to infer causal directions. Primary analyses utilized the Inverse Variance Weighted (IVW) method.
Robustness and Sensitivity Testing: To address violations of MR assumptions (e.g., pleiotropy), the study employed:
- Cochran's Q for heterogeneity.
- MR-Egger regression to detect directional pleiotropy.
- Weighted median and mode approaches.
- MR-CAUSE (Causal Analysis Using Summary Effect Estimates): A method specifically designed to distinguish causal effects from correlated pleiotropy arising from shared heritable factors.
- MR-Lap: To correct for biases related to the winner's curse, weak instruments, and sample overlap.
- Leave-one-out analyses: To ensure no single SNP drove the results.
Colocalization: Using the SuSiE (Sum of Single Effects) approach for fine-mapping, followed by coloc-SuSiE analysis, the authors tested whether ADHD and personality traits shared the same underlying causal variants within specific genomic loci, rather than merely being in linkage disequilibrium.

Key Results

Genetic Correlations: ADHD showed positive genetic correlations with Neuroticism ( $r_g = 0.32$ ), Extraversion ( $r_g = 0.18$ ), and Openness ( $r_g = 0.09$ ), and negative correlations with Agreeableness ( $r_g = -0.31$ ) and Conscientiousness ( $r_g = -0.22$ ).
Personality $\rightarrow$ ADHD (Vulnerability Model):
- Neuroticism: A robust causal effect was found where higher genetic liability to Neuroticism increases ADHD risk (IVW $\beta = 0.57$ , $p = 2.1 \times 10^{-21}$ ). This was supported by MR-CAUSE and weighted median methods, despite evidence of directional pleiotropy.
- Extraversion: Higher Extraversion was associated with increased ADHD liability (IVW $\beta = 0.39$ , $p = 1.3 \times 10^{-4}$ ), supported by MR-CAUSE and weighted median estimates.
- Conscientiousness: Lower Conscientiousness was associated with increased ADHD liability (IVW $\beta = -0.50$ , $p = 5.1 \times 10^{-4}$ ), supported by MR-CAUSE.
- Openness: No significant causal influence was detected in either direction.
ADHD $\rightarrow$ Personality (Scar Model):
- Agreeableness: ADHD genetic liability was found to have a negative causal effect on Agreeableness (IVW $\beta = -0.05$ , $p = 3.0 \times 10^{-4}$ ). This result was consistent across IVW, weighted median, and MR-CAUSE (which favored a causal model over a sharing model).
- Neuroticism: While MR-CAUSE suggested a potential small effect of ADHD on Neuroticism, instrument-based methods (IVW, MR-Egger) did not detect a significant effect, suggesting the effect is likely small or non-existent.
- Other Traits: No significant causal effects of ADHD on Extraversion, Conscientiousness, or Openness were detected.
Colocalization: Variant-level support was found for shared causal signals between ADHD and Neuroticism, Conscientiousness, and Agreeableness at specific loci (e.g., FOXP2 for Agreeableness; RNU6-334P and NIHCOLE for Neuroticism/Conscientiousness). No colocalization was found for Extraversion, likely due to limited fine-mapping resolution rather than a lack of shared signal.

Significance and Claims
The authors claim this study provides the first comprehensive, population-level genetic evidence distinguishing the directional relationships between ADHD and the Big Five personality traits using robust causal inference methods.

Dual Mechanism: The findings support a dual-mechanism model. The vulnerability model is strongly supported for Neuroticism, Extraversion, and Conscientiousness, indicating these traits may predispose individuals to ADHD. Conversely, the scar model is supported for Agreeableness, suggesting that ADHD liability may lead to reduced Agreeableness, potentially reflecting interpersonal difficulties.
Methodological Rigor: By integrating MR-CAUSE and colocalization, the study addresses limitations of previous work that could not adequately account for correlated pleiotropy or distinguish shared causal variants from linkage disequilibrium artifacts.
Clinical Implications: The results suggest that personality traits could serve as behavioral indicators of genetic risk for ADHD. The authors posit that future work might explore whether personality-informed interventions (e.g., emotion regulation for high Neuroticism) could improve ADHD outcomes, though they explicitly state this remains an open question for future research.

The paper concludes with modesty regarding its limitations, noting that findings are currently restricted to European ancestry, that the ADHD GWAS focused on childhood diagnoses, and that larger GWAS are needed to confirm smaller effects (such as the reverse effect of Agreeableness on ADHD) and to improve fine-mapping resolution.

Technical Summary: Testing Bidirectional Genetic Links Between ADHD and the Big Five Personality Traits

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