["Persistence" as possible psychogenetic endophenotype].

Abstract

For some human traits heritability estimates are well known based on results from twin studies. However, the study of connecting these characteristics to candidate genes in the Human Genome has just been started. The main goal of the recently formulated Human Fenom Project is to define "endophenotypes", characteristics that have considerable heritable component, and can be empirically measured with objective tools, standardized across cultures. Based on our recent findings the VNTR polymorphism in the coding region of the dopamine D4 receptor gene is a candidate gene of the "persistence" trait. Individuals carrying the 7-repeat polymorphism of this allele describe themselves as less persistent. In line with these results the 7-repeat polymorphism was associated to the "persistence" trait as measured by the Junior version of the TCI in a psychiatric sample of children diagnosed with ADHD. Based on these findings our main goal was to define an objective, behavioral measure which could be used as an "endophenotype" in genetic association studies. "Persistence" could be related to responsiveness in a reaction time task demanding sustained attention, for example. This hypothesis was tested using a sample of 35 healthy Caucasian subjects, participating in a extended cognitive reaction time task and filling out the TCI personality questionnaire. Non-invasive DNA sampling was used to determine the candidate polymorphism of the DRD4-VNTR. Results using self-report data replicated our previous findings: the 7-repeat polymorphism was significantly associated to lower "persistence" scores. Individual differences of reaction time were compared using the 7-repeat present/absent grouping as well. Results indicate that responses of individuals with the 7-repeat allele were significantly slower and more variable than of those without this candidate allele. Based on self-report and behavioural measures "persistence" trait is a possible endophenotype of psychogenetic associations.