Three genetic–environmental networks for human personality

Igor Zwir, Coral Del-Val, Javier Arnedo, Laura Pulkki-Råback, Bettina Konte, Sarah S. Yang, Rocio Romero-Zaliz, Mirka Hintsanen, Kevin M. Cloninger, Danilo Garcia, Dragan M. Svrakic, Nigel Lester, Sandor Rozsa, Alberto Mesa, Leo Pekka Lyytikäinen, Ina Giegling, Mika Kähönen, Maribel Martinez, Ilkka Seppälä, Emma RaitoharjuGabriel A. de Erausquin, Daniel Mamah, Olli Raitakari, Dan Rujescu, Teodor T. Postolache, C. Charles Gu, Joohon Sung, Terho Lehtimäki, Liisa Keltikangas-Järvinen, C. Robert Cloninger

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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.

Original languageEnglish
Pages (from-to)3858-3875
Number of pages18
JournalMolecular Psychiatry
Issue number8
StatePublished - Aug 2021


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