Visual masking deficits in schizophrenia: A view into the genetics of the disease through an endophenotype

Schizophrenia is a chronic disorder determined by a complex mix of genetic and environmental factors. To better understand the contributions of human genetic variation to schizophrenia, we performed a genome-wide association study of a validated endophenotype: a backward masking task, in which two vertical bars, slightly offset in the horizontal direction, are shortly presented to participants, who are asked to indicate the offset direction (left vs. right). The bars are followed by a mask, which makes the task difficult. The time between the bars and mask was determined in 214 schizophrenia patients, 113 first-order relatives, and 148 controls. In comparison to the response times observed in controls (42.1 ± 30.6 ms), performance was significantly reduced in healthy relatives (61.3 ± 57.3 ms), and more strongly deteriorated in schizophrenia patients (129.4 ± 113.2 ms), supporting the notion that masking is an endophenotype of schizophrenia. We genotyped all participants on the Infinium Global Screening Array with Multi-Disease drop in. To search for associations between human polymorphisms and our endophenotype, we performed a single-marker genome-wide association study using linear mixed model on log-transformed data, implemented in GCTA software. We did not identify any genome-wide significant association (p < 5E−8), indicating that common variants with strong effects are unlikely to contribute to the large inter-individual differences observed in schizophrenia-related visual masking deficits.