What’s your personality type?
Every day, we interact with a wide variety of people, each with unique personalities. According to a popular model in behavioral sciences known as the Big Five Model, also known as ‘OCEAN’, an individual’s personality can be defined across five dimensions: Openness, Conscientiousness, Extraversion, Agreeableness, and Neuroticism. The unique combination of these five dimensions shapes our distinct personalities and behaviors. Have you ever wondered how much our genetic inheritance, the DNA we receive from our parents, influences our personality? And what are these genetic factors? This question has been a hot topic in the scientific community for a long time.
Personality genetics
Genome-wide association studies (GWAS) is a popular choice of technique to study these complex behavioral traits, which are highly polygenic in nature. It involves scanning the genomes of large cohort of individuals to find single nucleotide polymorphisms (SNPs) or genetic markers linked to specific traits or diseases. In the last two decades, GWAS research studies conducted by different groups have provided insights into the genetics of personality. However, most studies have focused on neuroticism, and the understanding of the other four traits have been relatively limited and is based on much underpowered analysis.
Our study and findings
At Levey Lab, Yale School of Medicine and VA Healthcare, Connecticut, we attempted to address this challenge using the Million Veteran Program (MVP) cohort. VA’s Million Veteran Program is a national research program looking at how genes, lifestyle, military experiences, and exposures affect health and wellness in Veterans. In this Study, we have carried out GWAS of all five personality traits in a large sample of ~265,000 individuals from the MVP. Further, meta-analysis is performed by merging the obtained results with other publicly available Big Five studies including samples from UK Biobank, Genetics of personality consortium. This large sample (upto ~682,000) based meta-analysis identified 208, 14, 3, 2, and 7 independent genomic loci associated with neuroticism, extraversion, agreeableness, conscientiousness, and openness, respectively. 254 genes were found to be associated with at least one of the five personality traits.
With this vast amount of deduced genetic data from common SNPs associated with personality traits, we examined correlations among the different personality trait pairs solely based on their genetics. We found neuroticism has the highest negative genetic correlation with agreeableness out of all four other traits. After examining personality genetics at the SNP-level, investigations into gene and protein expression through Transcriptome-Wide Association Studies (TWAS) and Proteome-Wide Association Studies (PWAS) suggested altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT, and STX4 in neuroticism.
Like our analysis described above, most of the behavioral genetic studies are focused on European cohorts due to the sheer availability of European genetic data in different cohorts. It’s important to conduct GWAS analysis in diverse ancestry groups. We attempted investigating the differences in personality genetics with an African ancestry (AFR) cohort (N=30,000) GWAS from MVP. We found 2 loci (ARGAP24 & CCDC6) associated with agreeableness. While this is the first report of any AFR specific loci to be reported for personality, AFR GWAS study is still underpowered, and we need to work on increasing the AFR and other ancestry group samples sizes before we get to know any ancestry specific in-depth insights of personality genetics.
The most interesting findings: Personality and mental illnesses
Studying the genetics underlying personality traits has important implications in studying the biological relationship between different personality traits and various mental illnesses. Neuroticism, for instance, has been associated with disorders such as depression and schizophrenia. Most studies examining the relationship between different personality traits and mental illnesses have been guided by phenotypic analysis and have lacked biological/genetic inferences, primarily due to insufficient genetic data. Our current research fills this gap substantially. The comprehensive understanding of the genetic makeup of different personality traits revealed in this work provides a framework for exploring the genetic foundations of these associations for all five personality dimensions, not just neuroticism. Our findings indicate that the genetics of neuroticism are positively correlated with depression, anxiety, and manic behavior. Interestingly, agreeableness exhibited the strongest negative genetic correlation with these disorders, suggesting a potential protective role against these disorders. Subsequent conditional and mendelian randomization analyses supported these findings.
Conclusion
In summary, this work provides a comprehensive view of the crucial genetic factors that mediate the biology of various personality traits and their connections to psychiatric disorders. The study provides the genetic instruments to disentangle the influence of personality traits in studies of mental health conditions like depression, schizophrenia, anxiety, helping to better understand the genetic underpinnings of these disorders. Given the strong association between personality and mental health, the current research holds significant potential for assessing genetic predispositions to certain mental health disorders in individuals using methods like polygenic risk scores and thereby, can facilitate early interventions. Additionally, the knowledge gained from personality genetics has wider applications in pharmacogenomics field to guide the development of personalized drugs and treatments.
Outside the genetics lab, the key takeaway is that our personality plays a significant role in our mental health. Although the genetics that shape our unique personalities are majorly fixed, gaining a deeper understanding of our personality traits can help us become more aware of potential mental health risks. With this awareness, individuals and society can develop effective coping mechanisms to address these risks.
A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology
