Common variants of HTR1A and SLC6A4 confer the increasing risk of Schizophrenia susceptibility: A population-based association and epistasis analysis

Abstract

Schizophrenia (SZ) is a complex psychiatric disorder strongly influenced by genetic variants, some of which are associated with mood disorders. The neurotransmitter 5-hydoxytryptamine (5-HT) and its related biochemical factors have been shown to play a significant role in maintaining mood balance. Recent studies evaluating the association between SZ and genetic polymorphisms in a serotonin transporter (encoded by SLC6A4) and serotonin receptor 1A (encoded by HTR1A) show conflicting results. In this study, we performed a case-control association analysis using 4,000 individuals with Chinese-Han ancestry. Of these participants, 1,000 were SZ cases and 3,000 were healthy controls. Thirty-six single nucleotide polymorphisms (SNPs) located in SLC6A4 and HTR1A were genotyped in our 4,000 study samples. Of those, 33 polymorphic SNPs with a minor allele frequency >0.05 were used for further analysis. We found that rs878567 in HTR1A (asymptotic P-value=3.89×10-4, corrected P-value=0.0106) was significantly associated with SZ. Further haplotype-based analyses revealed that a two-SNP haplotype, rs2054847-rs140701 (TG) in gene SLC6A4, was significantly associated with SZ (P-value=1.63×10-4 and corrected P-value=0.002799). We did not identify any significant epistatic interactions between the two genes. Our findings provide supportive evidence that genetic polymorphisms in SLC6A4 and HTR1A may influence the risk of SZ in Han Chinese individuals.