The tetraspanins are a highly conserved superfamily of cell-surface membrane proteins known to be influential in diverse diseases and physiologic processes. High expression of TSPAN1, TSPAN8, or TSPAN2, for example, which are all in the same protein family as TSPAN18
, correlates positively with tumor progression 
, while mutation in TSPAN7 is associated with X-linked mental retardation 
Although earlier reports implicate TSPAN18
in susceptibility for SCZ 
, Ma et al. 
failed to confirm that association. In this case-control study of Han Chinese, we, too, find no statistically significant association between SCZ and the two TSPAN18
SNPs rs11038167 and rs11038172. Our analyses do reveal a statistically significant difference between patients with schizophrenia and healthy controls: the frequency of the “A” allele of rs835784 occurs at 31% in our SCZ samples and at 27% in controls. This finding confirms Yue et al.'s 
report that carriers of the A-allele of rs835784 are at 1.197-fold greater risk for SCZ than non-carriers.
It should be noted that this study's subjects were all recruited from Jiangsu province, while Yue et al.'s study sample was drawn from northern China (an area that includes Beijing, Tianjin, Hebei and Shandong), and Ma et al.'s from Hunan province. It is therefore possible that differences in their TSPAN18 polymorphism profiles could reflect regional differences not generalizable to all people of Han descent.
While a more definitive assessment of potential population stratification among Han Chinese subpopulations is not feasible in this study, we were able to compare SNP frequency distribution in different ethnic groups using dbSNP data from HapMap and the 1000-genomes studies. Our allele frequency analysis of these data for the three TSPAN18 SNPs revealed substantial differences among Asian, European, and African populations (). To identify precisely how ethnicity and geographic origin affect the distribution of genetic factors associated with schizophrenia, larger replication studies are needed.
Allele frequency distribution among different ethnic groups for the three SNPs in TSPAN18.
To summarize, this case-control study of a Han Chinese population validated a SNP locus in TSPAN18 reported by an earlier GWAS study and provided important evidence for the association of a particular variant of the TSPAN18 gene with increased SCZ susceptibility. Further studies to validate these findings on the molecular level are clearly warranted. Data from this study are available upon request.