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Six Loci Linked to Personality Traits in Meta-Analysis

NEW YORK (GenomeWeb) – Researchers have unearthed genetic correlations between personality traits and psychiatric disorders, according to a new study.

A team led by the University of California, San Diego's Chi-Hua Chen conducted a meta-analysis of genome-wide association studies that examined personality traits. Under the five-factor model of personality, there are five personality dimensions: extroversion, neuroticism, agreeableness, openness, and conscientiousness. Previous work, the researchers noted, has indicated that about 40 percent of variance in personality may be genetic.

As Chen and her colleagues reported in Nature Genetics today, they linked six genetic loci to these personality traits and examined their genetic ties to a handful of psychiatric disorders. They found, for instance, a high correlation between openness and schizophrenia and between extraversion and attention-deficit hyperactivity disorder.

"Researchers are only beginning to understand the genetics of personality and their relation to psychiatric disorders," they wrote in their paper.

The researchers drew on data collected by the consumer genomics firm 23andMe from 59,225 customers who completed a personality inventory. They also analyzed two datasets from the Genetics of Personality Consortium — one of 17,375 people that included data on agreeableness, conscientiousness, and openness, and one of 63,661 people that included data on extraversion and neuroticism. All participants were of European ancestry.

After combining the GWAS summary statistics, the investigators connected eight SNPs to personality traits, six of which they confirmed in three independent cohorts.

According to Chen and her colleagues, the strongest association they uncovered was between neuroticism and a region of 8p23.1, a four-megabase expanse that includes genes involved in innate immunity, the nervous system, cancer, and developmental neuropsychiatric disorders. The researchers noted that studies from the UK Biobank also identified a link between an inversion in this region and neuroticism.

At the same time, Chen and her colleagues uncovered an association between extraversion and a locus on 12q23.3 in WSCD2, which has been linked to temperament in bipolar disorder, as well as an association between extraversion and a SNP near PCDH15, which encodes a cadherin superfamily member.

All six of the SNPs the researchers identified fall in regions that have been linked to other phenotypes, including ones related to psychiatric disorders. For instance, they linked neuroticism to a variant in L3MBTL2, a gene that had previously been associated with schizophrenia. In addition, they linked extraversion to a variant in MTMR9, which has also been associated with response to antipsychotic medications.

In a pairwise analysis, the researchers examined the genetic correlations between the five personality traits and six psychiatric disorders, using data from the Psychiatric Genomics Consortium on schizophrenia, bipolar disorder, major depressive disorder, ADHD, and autism spectrum disorder, and data from the Genetic Consortium for Anorexia Nervosa.

This, they reported, uncovered numerous ties between personality traits and psychiatric disorders. For example, they noted that neuroticism was highly correlated with depression, while extraversion was linked with ADHD.

Through a principal components analysis, Chen and her colleagues found that openness, bipolar disorder, and schizophrenia cluster together. All three, the researchers noted, have been linked to increased creativity and dopamine activity. Likewise, conscientiousness, agreeableness, and extraversion clustered together, while neuroticism and depression formed their own grouping.

ADHD exhibited a high correlation with extraversion and low correlation with the other psychiatric disorders, save bipolar disorder, the researchers noted. This could suggest that ADHD or some subtypes of ADHD may be a variant of extraversion.

"These findings provide additional support for shared genetic influences between personality traits and psychiatric disorders and for the idea that personality traits and psychiatric disorders exist on a continuum in phenotypic and genomic space," the authors wrote. "Maladaptive or extreme variants of personality may contribute to the persistence of, or vulnerability to, psychiatric disorders and comorbidity."