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New Genetic Sites Associated With the “Big Five” Personality Traits

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Your DNA has long been known to play a role in shaping your personality. Now, researchers at Yale School of Medicine (YSM) have taken another step in determining exactly how by identifying a number of new genetic sites associated with specific personality traits. They published their findings in Nature Human Behavior on August 12.


Using data from the Million Veteran Program, researchers performed a genome-wide association study (GWAS) to identify genetic variations, called “loci,” associated with each of the “Big Five” personality traits: extraversion, openness, agreeableness, neuroticism, and conscientiousness. The researchers then combined these data with previous GWAS to perform a meta-analysis with almost 700,000 individuals, marking the largest GWAS for personality traits to date.


“We are a step closer in that process of increasing the sample size to be able to more clearly understand which variants are truly related to these personality traits,” says Daniel Levey, PhD, assistant professor of psychiatry at YSM and principal investigator of the study.

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The Big Five and novel loci

The Big Five personality traits are a scientifically based measure of personality that can be studied using self-reported assessments that indicate whether people score high or low in each of the five traits. Participants in the Million Veteran Program, a national research program that collects data including genetic information from veterans to better understand genes and health, completed these assessments in addition to providing a blood sample for genetic analysis.

Just because we’re finding these genetic variations doesn’t mean that these are things that are fated that you can’t change about your life.

Daniel Levey, PhD

By comparing personality assessment results with the analysis of variations in the participants’ DNA, Levey and his team found 62 new loci associated with neuroticism. They also identified loci for agreeableness for the first time. By combining their results with previously published data, they performed a meta-analysis to identify over 200 genetic loci across the five personality traits.


Even with the large number of genetic variations they found, Levey hopes that they will be able to further expand on these studies in the future, eventually increasing the number of participants to millions of people rather than hundreds of thousands and increasing the diversity of participants as well. Current studies of genes and personality have been largely made up of people with European ancestry.


“To be able to be confident in saying what direction of effect these variations have and what the actual precise effect of the variation is, we need to have vastly larger sample sizes,” Levey says. “Current human genetic studies are homogenous relative to the world populations. If you were able to bring in more diverse people and you were able to look at how associations in one population versus another overlap, it would give us a tighter definition.”

Genes, personality, and mental health

Levey and his team also investigated genetic correlations between personality traits and various mental health conditions. They found that there was a strong overlap between neuroticism, a personality trait marked by negative feelings, and depression and anxiety. People with high agreeableness, a personality trait marked by a tendency to get along well with others, were less likely to experience these conditions. These associations are already well understood from a psychiatric perspective, but Levey’s findings provide additional genetic confirmation.


Priya Gupta, PhD, postdoctoral associate in Levey’s lab and first author of the manuscript, says that “although genetics are largely beyond our control, gaining a deeper understanding of our personality traits can help us become more aware of potential mental health risks and develop effective coping strategies to address these risks.”


But just because there is a genetic basis for the associations between personality traits and certain mental health conditions, it doesn’t mean that those associations last a lifetime, Levey says.


“Your personality will adapt and change over time, so there’s a temporal relationship which we’re not necessarily capturing with the cross-sectional way we’re looking at personality in our study,” he says. “Just because we’re finding these genetic variations doesn’t mean that these are things that are fated that you can’t change about your life.”


Levey hopes that personality studies such as these might one day be useful in informing early treatment for mental health conditions.


“When you’re looking at these personality traits that are more predisposed to later developing mental illness, that could be a prodromal [a period of subclinical symptoms] look at who might be at higher risk, and then maybe it might be grounds for intervention,” he says. “Even if we can measure genetically the associations to traits like neuroticism, that doesn’t mean that you can’t alter your strategies for dealing with life in ways that could help you achieve better outcomes.”


Reference: Gupta P, Galimberti M, Liu Y, et al. A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology. Nat Hum Behav. 2024. doi: 10.1038/s41562-024-01951-3


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