The molecular genetic architecture of human personality: beyond self-report questionnaires

Abstract

Molecular genetic studies of personality began with two high impact papers in 1996 that showed provisional associations between the dopamine DRD4 exon III repeat region and Novelty Seeking/Extraversion. These first two reports were shortly followed by an investigation linking Neuroticism/Harm Avoidance with the serotonin transporter (SLC6A4) promoter region polymorphism (5-HTTLPR). In the ensuing decade, thousands of subjects have been studied for association between these genes and personality, assessed by using self-report questionnaires, with erratic success in replication of the first findings for Novelty Seeking (DRD4) and Harm Avoidance (5-HTTLPR). Small effect sizes characteristic of non-Mendelian traits, polygenic patterns of inheritance and true heterogeneity between studies confound attempts to reach a consensus regarding the role of common polymorphisms in contributing to personality domains. Nevertheless, the current state of personality genetics is far from being bleak. Several new paradigms especially functional neuroimaging or 'imaging genomics' have strengthened the connection between 5-HTTLPR and anxiety-related personality traits. The demonstrations that early environmental information can considerably strengthen and even uncover associations between genes and behavior (Caspi's seminal studies and more recently the demonstration that early environment impacts on DRD4 and Novelty Seeking) are notable and herald a new era of personality genetics. Finally, consideration of the broader phenotypic expression of common polymorphisms (e.g. the 'social brain', altruism, etc.) and the use of new experimental paradigms including neurophysiological, neuropsychological and computer games that go beyond the narrow self-report questionnaire design will enable a deeper understanding of how common genetic polymorphisms modulate human behavior. Human personality, defined by Webster as the quality or state of being a person or the complex of characteristics that distinguishes an individual, surely requires a more encompassing view towards understanding its complex molecular genetic architecture.

Gene–environment correlations: a review of the evidence and implications for prevention of mental illness

“…Meta-analyses are beginning to identify small but consistent associations between specific genetic variants and personality characteristics. 71 For example, a number of meta-analyses have identified an association between 5-HTTLPR and the personality trait of neuroticism. [72][73][74][75] Not only is neuroticism a strong correlate of depression (for a review, see Klein et al 76 ), but individuals who score high on neuroticism are prone to experience stressful life events, particularly those of an interpersonal nature (e.g., Headey and Wearing, 77 Kendler et al, 78 Van Os and Jones 79 ).…”

Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

“…5 Other models of personality, such as the Five Factor Model or Eysenck's Extraversion and Neuroticism dimensions, have different theoretical underpinnings but have been shown to access very similar aspects of human behavior. 6 Neuropsychological and psychopharmacological studies have contributed to our understanding of the neural basis of personality and this work continues apace with new tools. Two recent avenues of inquiry have revealed promising results; first, functional neuroimaging has been used to correlate brain activation during behaviorally relevant tasks with personality scores across individuals.…”

“…However, even for the most widely studied such gene, a promoter variant in the serotonin transporter (5-HTTLPR), a consistent picture has not emerged. 6,12 One likely reason for small effect sizes on the level of behavior is that genetic variation must be mediated by functional alterations on the neural systems level. 13 This suggests that progress can be made by combining these two strategies through studying the impact of genetic variation linked to personality on human brain structure and function.…”

Biochemistry and molecular biology techniques for person characterization

“…Additionally, this is a relatively highly polymorphic locus, increasing our chances of detecting differences among the different samples. The VNTR used here is localized in exon 3 from the D4 dopamine receptor and the presence of long alleles (mainly the seven-repeats allele) has been correlated with high levels of novelty seeking (characterized as impulsive, exploratory, fickle, excitable, quick-tempered, and extravagant personality) ( [7], review in [8]). Moreover, the higher frequency of seven-repeats allele has also been associated with the abuse of substances [9].…”

“…However, this kind of information has to be carefully given to the students to avoid misinterpretations and simplifications of the data. It is the responsibility of the instructor to clearly remark two points: (i) some authors have questioned the association of DRD4 alleles with personality traits or abuse of substances (see review in [10]) because of the failure of other authors to replicate these studies with other samples; (ii) in case this association was true, the DRD4 alleles would have a very weak effect, being the contribution of the environment and other genes the most important factor in traits related with the personality or the abuse of substances [8,10]. …”