Genome wide association study of intermediate phenotypes of schizophrenia

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Many patients with schizophrenia experience a decline in intellectual functioning. We conducted a genome-wide association study (GWAS) of cognitive decline in 166 patients with schizophrenia. Cognitive decline (subtraction of JART score from full-scale IQ) was -16.1.The strongest association was observed at rs7157599 on chromosome 14, a missense polymorphism (Asn8Ser) in the DEGS2 gene (p=5.4×10-7). Replication analysis using the National Institute of Mental Health Clinical Brain Disorders Branch sample revealed a directionally consistent trend association of genotype for a proxy of the top SNP. Although the study should be replicated with a larger sample size, our results indicate that the measurement of cognitive decline in schizophrenia as a quantitative phenotype (in conjunction with GWAS) could be a gene discovery tool.