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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.

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