Uncovering the complex genetics of human temperament

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Zwir , I , Arnedo , J , Del-Val , C , Pulkki-Raback , L , Konte , B , Yang , S S , Romero-Zaliz , R , Hintsanen , M , Cloninger , K M , Garcia , D , Svrakic , D M , Rozsa , S , Martinez , M , Lyytikäinen , L-P , Giegling , I , Kähönen , M , Hernandez-Cuervo , H , Seppälä , I , Raitoharju , E , de Erausquin , G A , Raitakari , O , Rujescu , D , Postolache , T T , Sung , J , Keltikangas-Jarvinen , L , Lehtimäki , T & Cloninger , C R 2020 , ' Uncovering the complex genetics of human temperament ' , Molecular Psychiatry , vol. 25 , no. 10 , pp. 2275-2294 . https://doi.org/10.1038/s41380-018-0264-5

Title: Uncovering the complex genetics of human temperament
Author: Zwir, Igor; Arnedo, Javier; Del-Val, Coral; Pulkki-Raback, Laura; Konte, Bettina; Yang, Sarah S.; Romero-Zaliz, Rocio; Hintsanen, Mirka; Cloninger, Kevin M.; Garcia, Danilo; Svrakic, Dragan M.; Rozsa, Sandor; Martinez, Maribel; Lyytikäinen, Leo-Pekka; Giegling, Ina; Kähönen, Mika; Hernandez-Cuervo, Helena; Seppälä, Ilkka; Raitoharju, Emma; de Erausquin, Gabriel A.; Raitakari, Olli; Rujescu, Dan; Postolache, Teodor T.; Sung, Joohon; Keltikangas-Jarvinen, Liisa; Lehtimäki, Terho; Cloninger, C. Robert
Contributor: University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, University of Oulu
University of Helsinki, Medicum
Date: 2020-10
Language: eng
Number of pages: 20
Belongs to series: Molecular Psychiatry
ISSN: 1359-4184
URI: http://hdl.handle.net/10138/320524
Abstract: 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.
Subject: PERSONALITY-TRAITS
REGULATORY NETWORK
EPISODIC MEMORY
HARM AVOIDANCE
HEALTHY TWIN
WEB SERVER
ASSOCIATION
VARIANTS
5-HTTLPR
NOVELTY
515 Psychology
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