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Uncovering the complex genetics of human temperament

Artikel i vetenskaplig tidskrift
Författare Igor Zwir
Javier Arnedo
Coral Del-Val
Laura Pulkki-Råback
Betina Konte
Sarah S. Yang
Rocio Romero-Zaliz
Mirka Hintsanen
Kevin M. Cloninger
Danilo Garcia
Dragan M. Svrakic
Sandor Rozsa
Maribel Martinez
Leo-Pekka Lyytikäinen
Ina Giegling
Mika Kähönen
Helena Hernandez-Cuervo
Ilkka Seppälä
Emma Raitoharju
Gabriel A. de Erausquin
Olli Raitakari
Dan Rujescu
Teodor T. Postolache
Joohon Sung
Liisa Keltikangas-Järvinen
Terho Lehtimäki
C. Robert Cloninger
Publicerad i Molecular Psychiatry
Volym In Press
Nummer/häfte In Press
Sidor In Press
ISSN 1359-4184
Publiceringsår 2018
Publicerad vid Psykologiska institutionen
Sidor In Press
Språk en
Länkar https://doi.org/10.1038/s41380-018-...
Ämnesord Personality, Genetics, Temperament, Machine Learning.
Ämneskategorier Psykiatri, Genetik, Psykologi

Sammanfattning

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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