University of Oulu

Zwir, I., Arnedo, J., Del-Val, C. et al. Uncovering the complex genetics of human temperament. Mol Psychiatry 25, 2275–2294 (2020).

Uncovering the complex genetics of human temperament

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Author: Zwir, Igor1,2; Arnedo, Javier1,2; Del-Val, Coral2;
Organizations: 1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
2Department of Computer Science, University of Granada, Granada, Spain
3Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
4Department of Psychiatry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
5Department of Epidemiology, School of Public Health, Institute of Health and Environment, Seoul National University, Seoul, Korea
6Unit of Psychology, Faculty of Education, University of Oulu, Oulu, Finland
7Anthropedia Foundation, St. Louis, MO, USA
8Department of Psychology, University of Gothenburg, Gothenburg, Sweden
9Blekinge Centre of Competence, Blekinge County Council, Karlskrona, Sweden
10Fimlab Laboratories, Department of Clinical Chemistry, Faculty of Medicine and Life Sciences, Finnish Cardiovascular Research Center-Tampere, University of Tampere, Tampere, Finland
11University Clinic, Ludwig-Maximilian University, Munich, Germany
12Department of Clinical Physiology, Faculty of Medicine and Life Sciences, Tampere University Hospital, University of Tampere, Tampere, Finland
13Department of Psychiatry and Neurosurgery, University of South Florida, Tampa, FL, USA
14Department of Psychiatry and Neurology, Institute of Neurosciences, University of Texas Rio-Grande Valley School of Medicine, Harlingen, TX, USA
15Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
16Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
17Rocky Mountain Mental Illness, Research, Education and Clinical Center for Veteran Suicide Prevention, Denver, CO, USA
18Department of Psychological and Brain Sciences, School of Arts and Sciences, and Department of Genetics, School of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3 MB)
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Language: English
Published: Springer Nature, 2020
Publish Date: 2020-10-06


Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic–phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37–53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.

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Series: Molecular psychiatry
ISSN: 1359-4184
ISSN-E: 1476-5578
ISSN-L: 1359-4184
Volume: 25
Pages: 2275 - 2294
DOI: 10.1038/s41380-018-0264-5
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
1184 Genetics, developmental biology, physiology
Funding: The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association: and EU Horizon 2020 (grant 755320 for TAXINOMISIS). The American Foundation for Suicide Prevention supported the study of healthy Germans. The national Healthy Twin Family Register of Korea supported the study of healthy Koreans. The Anthropedia Foundation and the Spanish Ministry of Science and Technology TIN2012-38805 and DPI2015-69585-R including FEDER funds supported this collaboration.
Copyright information: © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit