Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study
Year: 2017
Type: article
Study design: Observational Study
Abstract: Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophreniaN=230, schizoaffective disorderN=155, psychotic bipolar disorderN=206 and healthy controlsN=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across participants, sensorimotor processing at pursuit initiation was significantly associated with a single nucleotide polymorphism inIPO8(12p11.21,P=8 × 10−11), whereas suggestive associations with sustained pursuit maintenance were identified with SNPs inSH3GL2(9p22.2,P=3 × 10−8). In participants of predominantly African ancestry, sensorimotor processing was also significantly associated with SNPs inPCDH12(5q31.3,P=1.6 × 10−10), and suggestive associations were observed withNRSN1(6p22.3,P=5.4 × 10−8) andLMO7(13q22.2,P=7.3x10−8), whereas antisaccade error rate was significantly associated with a non-coding region at chromosome 7 (P=6.5 × 10−9). Exploratory pathway analyses revealed associations with nervous system development and function for 40 top genes with sensorimotor processing and pursuit maintenance (P=4.9 × 10−2–9.8 × 10−4). Our findings suggest novel patterns of genetic variation relevant for brain systems subserving eye movement control known to be impaired in psychotic disorders. They include genes involved in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous system development and function.
Source: Translational Psychiatry
DOI: 10.1038/tp.2017.210
Institutions: University of Münster, University of Minnesota, Minnesota Supercomputing Institute, University of Chicago, Broad Institute, Harvard University, Stanley Center for Psychiatric Research, Northwestern University, University of Lübeck, University of Georgia, Beth Israel Deaconess Medical Center, Hartford Hospital, Yale University, The University of Texas Southwestern Medical Center, University of Cincinnati
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
Awards: G1044130170, Schizophrenia Pharmacogenetics: cognition and symptom response to antipsychotics, G208937423, G2241124166, 1/5 Bipolar-Schizophrenia Network for Intermediate Phenotypes 2 (B-SNIP 2) - Resu, G2458313802, G4136061041, G4863277230, G4991243177, G568434048, G5926081180, G5938683149, G6528626969, G661573911, G7810676501, 3/5 Bipolar-Schizophrenia Network for Intermediate Phenotypes 2 (BSNIP-2), Yale Clinical and Translational Science Award
OpenAlex ID: W2765680938