9 Dec 2016
by Pat McCaffrey
The largest genomewide association study (GWAS) to date of the “big five” personality traits has revealed several loci significantly associated with neuroticism and extraversion. The study also found new genetic correlations between personality traits and psychiatric disorders, including schizophrenia, supporting the idea of a shared genetic basis for complex personality traits and psychiatric disease.
The work was published online December 5 in Nature Genetics.
In the study and associated meta-analysis, Chi-Hua Chen at the University of California, San Diego, and collaborators looked at the personality dimensions of extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience in new and previously published cohorts. New data from 98,725 customers of the consumer genetics company 23andMe were combined with data from the Genetics of Personality Consortium (de Moor et al, 2012; GPC et al., 2015), the UK Biobank (Smith et al., 2016), and deCODE Genetics, an Iceland-based human genetics company. In the final meta-analysis, between 123,132 and 260,861 subjects were included per trait.
Previously, a handful of SNPs had been identified in personality studies, but they had been hard to replicate. The new work identified eight new single nucleotide polymorphisms (SNPs) for three personality traits—six held up in a replication cohort, and two just missed significance. The strongest association was between neuroticism (a trait characterized by negative emotions such as anxiety and fear) and an SNP at 8p23.1, which replicated a previous report from the UK study.
Some schizophrenia-related genes popped out in the analysis: L3MBTL, one of hundreds of genes implicated in the latest schizophrenia GWAS (see SRF related story), was significantly associated with neuroticism, whileMTMR9, a potential player in adverse antipsychotic effects (Aberg et al., 2010), was linked to extraversion. MTMR9 represents the first gene to be found for that personality trait.
“People have doubted whether genes for personality could be identified, and this study confirms (yet again) that once sample size crosses a threshold (where the threshold might be >100,000 subjects), we can find SNPs that are causal or in linkage disequilibrium with causal variants,” commented Dorret Boomsma of Vrije Universiteit in Amsterdam in an email to SRF. Boomsma was not involved in the current analysis, but the study made use of data from 80,000 subjects in the Genetics of Personality Consortium, which she heads.
The study “shows the value of the earlier studies of the genetics of personality consortia that made their complete sets of results available for others (I hope that will also be the case for the current paper). The meta-analysis approaches developed in the genetics community can make optimal use [of] new and existing GWA studies, leading to real progress,” Boomsma wrote.
The five personality domains are not independent traits—in people, phenotypic measures of openness, agreeableness, conscientiousness, and extraversion positively correlate with each other and negatively correlate with neuroticism. Chen and colleagues found that the genetic correlations followed the same pattern but appeared even stronger, reflecting the shared genetic underpinnings of the traits.
To expand the analysis to psychiatric disorders, the researchers pooled their personality data with genetic information about six conditions: schizophrenia, bipolar disorder, major depression, ADHD, anorexia nervosa, and autism. They calculated genetic correlations and performed a principal component analysis of the entire data set.
As expected, the analysis picked up significant genetic correlation between depression and neuroticism. The correlation, the strongest one in the study, confirms genetic data from recent GPC studies and agrees with clinical data showing links between neuroticism and major depression and anxiety.
The study also found a new correlation between extraversion and ADHD, which Chen thinks may go along with overlapping features of the phenotypes. “One key feature of extraversion personality is a high level of activity, and while there are different subtypes of ADHD, some also show high activity,” she told SRF.
A third relationship, one that Chen said at first she found surprising, linked openness to experience with schizophrenia and bipolar disorder. However, both have been linked to higher dopamine levels, she says, which might provide a common basis for the two.
“These results show that there are a number of genetic ‘dimensions’ in the population with a continuous distribution that cause variation in traits that were considered dichotomous and in the medical domain of psychiatry, as well as in traits that were considered as belonging to the psychology domain,” Boomsma commented. She compared the current study to work showing a genetic dimension that influences risk of schizophrenia, as well as creativity (Power et al., 2015).
Exactly which genes underlie these domains and how they might be linked causally to personality traits and psychiatric disorders remains to be seen. In addition, the SNPs uncovered to date account for a tiny fraction of the heritability of these traits, indicating that there are many other genes waiting to be identified. “This is only the beginning of discovering genes related to personality traits or these complex psychiatric phenotypes,” said Chen.