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. © 2015 Wiley Periodicals, Inc.

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

“…and Zhou et al 34,. the significant signal of rs878567 was captured in the studies of Lin et al 35. and ours.…”

“…So far, some studies have investigated the association of HTR1A gene with SCZ in different populations including American, Korean, Japanese and Han Chinese populations2829303132333435, and the significant association was found in American29, Japanese33 and Han Chinese populations3435. Thus, the association of HTR1A gene with SCZ is not specific to a certain ethnic group.…”

“…HTR1A is the most abundantly expressed 5-HT receptor subtype in the mammalian brain, and HTR5A is expressed in the central nervous system, a significant portion of cortical pyramidal neurons2627. Previous studies have investigated the association between only a few HTR1A variants and SCZ, but they have produced conflicting results2829303132333435. So far, HTR5A has been studied less than other HTRs .…”

Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm

“…The HTR1A rs878567 SNP is located in the 3′-UTR of the 5-HT 1A receptor close to the splice site, and is in strong linkage disequilibrium with the rs6295 promoter polymorphism. 61 The rs878567 polymorphism has been associated with major depression, 46,47 schizophrenia, 194,195 psychosis 196 and depression after childhood physical abuse. 197 While many of these associations are similar to those for rs6295, the association with schizophrenia and psychosis was not as robust for rs6295.…”

Comprehensive Analysis of Complement Genes in Patients with Atypical Hemolytic Uremic Syndrome

“…The called variants were further reviewed in databases and analyzed in 100 local healthy controls. Commons variants were excluded, which were defined as variants with a minor allele frequency (MAF) value of >3% in the Asian population based on the 1000 Genomes Project (April 2012) or a frequency of >1% in the local control cohort [16] .…”