Uncovering the complex genetics of human temperament
Metadatos
Afficher la notice complèteAuteur
Zwir Nawrocki, Jorge Sergio Igor; Arnedo Fernández, Francisco Javier; Val Muñoz, María Coral Del; Romero Zaliz, Rocio CelesteEditorial
SpringerNature
Date
2018-10-02Referencia bibliográfica
Zwir, I., Arnedo, J., Del-Val, C., Pulkki-Råback, L., Konte, B., Yang, S. S., ... & Svrakic, D. M. (2020). Uncovering the complex genetics of human temperament. Molecular psychiatry, 25(10), 2275-2294. [DOI: 10.1038/s41380-018-0264-5]
Résumé
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