Evaluation of association of common variants in HTR1A and HTR5A with schizophrenia and executive function

The 5-HT1A receptor (HTR1A) and the 5-HT5A receptor (HTR5A) are key 5-HT receptors with distinct inhibitory functions. Studies have been conducted to investigate the association of a few HTR1A polymorphisms with schizophrenia, producing conflicting results, and the relationship between HTR5A and schizophrenia has not yet been well investigated. We aimed to examine the association of HTR1A and HTR5A with schizophrenia and executive function. The study included a discovery stage with 1,115 patients and 2,289 controls and a replication stage with 2,128 patients and 3,865 controls. A total of 30 common SNPs in HTR1A and HTR5A were genotyped in the discovery stage, and significantly associated SNPs were genotyped in the replication stage. We identified that two SNPs (rs878567 in HTR1A and rs1800883 in HTR5A) were significantly associated with schizophrenia in both datasets, and similar results were observed in imputation and haplotype association analyses. Moreover, we found that SNP rs1800883 significantly interacted with executive function when processing the perseverative error of Wisconsin Card Sorting Test in patients. Our results provide further supportive evidence of the effect of HTR1A and HTR5A on the etiology of schizophrenia and suggest that the selected genetic variations in HTR5A may be involved in impaired executive function.