Association of Neuregulin 1 rs3924999 with oculomotor endophenotypes for schizophrenia in healthy volunteers

Abstract

Neuregulin 1 (NRG1) has been identified as one of the leading schizophrenia candidate genes. However, its functional mechanisms and its effects on neurocognition remain unclear and the path from NRG1 to schizophrenia has not yet been fully mapped. In this study we use two well established oculomotor endophenotypes, the antisaccade (AS) and smooth pursuit (SPEM) tasks, to investigate the functional mechanisms of a single nucleotide polymorphism in NRG1 (rs3924999) at the neurocognitive level in a healthy population. 122 healthy Caucasian volunteers were genotyped for NRG1 rs3924999 and underwent infrared oculographic assessment of AS and SPEM (at target velocities of 12, 24 and 36°/s). Additionally, self-report questionnaires of schizotypy, neuroticism, attention deficit hyperactivity, and obsessive-compulsive traits were included. Significant effects of NRG1 genotype with age and gender as covariates were found for AS amplitude gain (p<0.01) and AS spatial error (p=0.01), with an increasing number of A alleles being associated with increasingly worse performance. No significant associations were found for other AS and SPEM variables or questionnaire scores. These findings indicate that NRG1 rs3924999 affects spatial accuracy measures of the AS task, suggesting an influence of the gene on the neural mechanisms underlying visuospatial sensorimotor transformations. This is a mechanism that has previously been found to be impaired in schizophrenia patients and their relatives.