Three genetic-environmental networks for human personality

Abstract

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences.

Fig. 1

The phenotypic architecture of personality. a Relationships among Temperament and Character Sets are naturally partitioned into three subnetworks using NMF (bidirectional-clustering) techniques: Creative-Reliable (violet), Organized-Reliable (blue), and Emotional-Unreliable (orange). b Relationships among SNP sets associated with Temperament and Character Sets composing the three networks shown in a: self-awareness (violet), self-control (blue), and emotional reactivity (orange)

Fig. 2

Relationships among Temperament and Character Sets composing the three networks shown in Fig. 1. a The Creative-Reliable subnetwork (light violet, violet) contains primarily Character Sets with creative subjects, who also display a reliable temperament. b The Organized-Reliable subnetwork (blue, violet) primarily contains Character Sets with organized subjects, who also display reliable temperament. c The Emotional-Unreliable subnetwork (green, black, and orange) contains Character Sets with dependent and apathetic subjects, who also display sensitive and antisocial temperaments. d The hierarchical organization of personality: temperament and character scales and subscales, sets of subscales (see Table S3), profiles, and networks

Fig. 3

Evaluation of the probability of health measured for Temperament and Character associations in the three phenotypic subnetworks using ANOVA statistics (p value < 1E−20), and T-test among the three subnetworks. The three networks, Creative-Reliable, Organized-Reliable, and Emotional-Unreliable, significantly differ from each other (p value < 1E−04) in their probability of well-being (a) and ill-being (d). b, e Evaluation of probability of health in Temperament and Character Sets and their relationships with SNP Sets using ANOVA statistics. b Well-being and e Ill-being evaluated for Temperament and Character Sets with respect to their profiles. c, f Surfaces representing the health function of the uncovered relationships between Temperament and Character Sets. The probability of health (z-axis; red high; green: low) was calculated based on the distribution of the status of subjects within each relationship, and the surface was plotted interpolating the relation domains. The order adopted for plotting relationships are calculated based on clustering shared subjects in Character (x-axis) and in Temperament (y-axis) Sets using Hypergeometric statistics (see “Method” section). (Close-located sets in an edge share more subjects than those located far away.) c Well-being surface. f Ill-being surface

Fig. 4

a Correlation between the phenotypic (Fig. 1a) and the genotypic (Fig. 1b) networks (p < 6E−52, Hypergeometric statistics). Color codes indicate low (red) to high (green) statistical significance. The size of the circles indicates the number of coincident phenotypic–genotypic relationships. b Relationships among key genes associated with Temperament and Character Sets that discriminate the three networks shown in Fig. 1a, b: self-awareness (violet), self-control (blue), and emotional reactivity (orange). (See AND/OR relationships in Fig. S5.) c Types of genetic variants mapped by SNP sets associated with character: specific molecular consequences [genes related only to character sets (green) were less often protein coding and more often RNA genes than those also associated with temperament sets (red color), or genes related to both character and temperament exhibit higher proportion of protein-coding genes. See subtypes in Fig. S4B]. d Relationships among environmental sets associated with Genotypic subnetworks (Fig. 1). Environmental sets can belong to one or more networks